The in vitro and in vivo antibacterial activites of cefuroxime axetil (CXM-AX), the 1-acetoxyethyl ester of cefuroxime (CXM), were investigated in comparison with those of CCL, CEX and AMPC. CXM showed a broad antibacterial spectrum against both gram-positive and gram-negative bacteria. Among them, S. pyogenes, S. pneumoniae, C. freundii, S. marcescens, P. rettgeri, M. rnorganii, P. stuartii and P. cepacia were extremely susceptible, but P. aeruginosa was resistant to CXM. CXM was also active against most of β-lactam resistant strains but not active against CXase producing strains. As to the protective effects in experimental infections with various bacteria, CXM-AX was more effective than CEX but not as effective as CCL.

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MICs₈₀ of cefuroxlme (CXM). that is the actlve moiety Of the oral prodrtlg, cefuroxime axetiI CXM.AX), for 24 to 59 clinical isolates of S. aureus, methicillin-and cephem-resisant S. aureus (MRSA). S. epidermidis, β-streptococci, S pneumomiae. E. coli carrying R plasmids, K pneumoniae, P mirahilis, P. vulgaris, m morganii, P. rettgeri, C. freucndii, E. cloacae, S.marcescens. P. aeruginosa, X. maltophilia, A. calcmceticus, ampicillin-resistant H. influenzae, and B. fragilis were 6.25, >100, 100, 0.05, 0.1, 6.25, 3. 13, 1.36, >100, 100, 25, 25, >100, >100, >100, >100, 50, 0.78 and 100 μg mi, respeetively.
The binding affinity of CXM to the PBPs, the sites of action of sensitive S.aureus 209 P, E. coli NIHJ JC-2, and S. marcescens 13 was as strong as that of cefmetazole (CMZ). CXNI bound more strongly to the PBPs of P. vulgaris 33 thall CMZ but more weakly to the PBPs of NIRSA than CMZ CXM manifested only weak synergy of bactericidal effect with the serum complement, but the synergy with cultured mouse macrophages was found tO be strong showing that the macrophages engulfed well E. coli cells and digested rapidly in the presence of higher than 14 of MIC Of CXM.

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The in vitro and in vivo antibacterial activity of Cefuroxime axetil (CXM-AX, SN 407), a new oral cephalosporin, was evaluated, and the following results were obtained.
1) In the studies using the standard strains, Cefuroxime (CXM) showed a broad spectrum of antibacterial activity against Gram-positive and Gram-negative organisms which was comparable or superior to that of CEX, ABPC, CCL and CFT. No difference was observed in the antibacterial activity between CXM, obtained through hydrolysis of CXM-AX with esterases, and CXM itself.
2) CXM showed high activity against clinical isolates of 13 species, especially against strains of S. pneumoniae, S. pyogenes, H. influenzae and N. gonorrhoeae.
3) CXM possessed better penetrability through outer membrane, compared with CCL and CEX, and its bactericidal effect was maintained for a long time.
4) In mice with experimental infections, CXM-AX exerted excellent therapeutic effect. In infections caused by Gram-positive organisms (e. g. S. aureus, S. pneumoniae and S. pyogenes), M. morganii and C. freundii in particular, therapeutic effect of CXM-AX was superior to those of CCL and CEX.

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Antibacterial activity of cefuroxime was tested against 71 reference strains of anaerobic bacteria (including genera Peptostreptococczts, anaerobic Streptococcus, Veillonella, Eubacterium, Propionibacterium, Bifidobacterium, Lactobacillus, Clostridiunz, Bacteroides and Fusobacterium) in comparison with that of cefaclor and cephalexin.
Antibacterial activity of cefuroxime was superior to that of cefaclor and cephalexin against anaerobic bacteria.
Cefuroxime, however, showed relatively low activity (MIC≥100 μg/ml) against beta -lactamase producing strains of Bacteroides fragilis group.

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We investigated the effects of cefuroxime axetil (CXM-AX) on bacterial normal flora in the intestine of 5 healthy male volunteers given the drug in the oral doses of 250 mg three times daily for 16 consecutive days. Some species of anaerobic bacteria decreased, and Enterococcus faecalis and Bacillus increased, however these changes returned to normal soon after the end of the dosing period.
No diarrhea occurred in any of the 5 volunteers given the drug orally. However, a small number of Clostridium difficile were detected in 3 volunteers either during or at the end of the dosing period.

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The in vitro and in vivo antibacterial activities of cefuroxime axetil (CXM-AX; SN 407), a prodrug of cefuroxime, were compared with those of cephalexin (CEX), cefaclor (CCL), and amoxicillin (AMPC). The following results were obtained.
CXM (the active form of CXM-AX) had broad antibacterial spectrum against gram-positive and gram-negative organisms, but showed low antibacterial activity against Serratia and glucose non-fermentative organisms. The antibacterial activities of CXM against clinically isolated gram-positive organisms were either similar or inferior to those of AMPC, but were superior to those of CEX and CCL. The antibacterial activities of CXM against gram-negative organisms, such as Escherichia coli, Klebsiella pneumoniae, P. mirabilis, Haemophilus influenzae, and Acinetobacter calcoaceticus, were inferior to those of AMPC or CCL, but were superior to those of CEX. Moreover, CXM was more active than these comparators against other gram-negative organisms.
The antibacterial activity of CXM was only slightly affected by the pH of the medium, the addition of horse serum, and the inoculum size.
The therapeutic efficacy of CXM-AX against experimental intraperitoneal infections caused by Streptococcus pneumoniae, S. pyogenes and E. coli in mice was either comparable or superior to that of CCL and superior to that of CEX. Against the infections with Staphylococcus aureus, K. pneumoniae, Enterobacter cloacae and Proteus mirabilis in mice, the therapeutic efficacy of CXM-AX was either comparable or superior to that of CEX but inferior to that of CCL.
In experimental respiratory tract infections with Klebsiella pneumoniae in mice, CXM-AX demonstrated efficacy comparable to CCL and superior to CEX. Therapeutic efficacy of CXM-AX against experimental urinary tract infections in mice was superior to that of CEX and CCL against the infections with E. coli, slightly inferior to that of CCL and superior to that of CEX against the infections with K. pneumoniae.

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Acute toxicity of cefuroxime axetil (CXM-AX), an oral prodrug of cefuroxime, was investigated, and the results are summarized as follows;
(1) Neither death nor any specific symptom was observed after the oral administration of CXM-AX in mice and rats even at the maximum dose that could be administered (3 g/kg with1% CMC used as vehicle, or 10 g/kg with olive oil used as vehicle).
(2) In rabbits orally given CXM-AX, general weakness was observed and LD₅₀ valuewas about. 0.2g/kg.
(3) After the intraperitoneal or subcutaneous injection in mice and rats, local symptoms, e.g. adhesion of abdominal organs (in i. p. group) and damage of skin at injection site (in s. c. group), which were considered to be caused by the administration of large amount of suspension, were, observed.

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Acute toxicity of cefuroxime axetil (CXM-AX) was investigated in 21-day-old mice and 14-and 21-day-old rats by oral, subcutaneous and intraperitoneal administration. The results are summerized as follows;
(1) Major general symptoms observed were suppression of spontaneous movement and bradypnea, which were considered not to be specific to CXM-AX, but to be generally induced by administration of large amount of the test sample.
(2) Some other changes were observed depending on the administration route, i. e. retention of the antibiotic in the stomach (in p. o. group) or in the subcutaneous injection site (in s. u. group), damages of skin and subcutaneous tissues at the injection sites (in s. c. group) and adhesion of abdominal organs to each other (in i. p. group).
(3) LD₅₀ values of the drug in the young animals ranged from 1/3 of, to similar value to those in 5-week-old animals.

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A study on subacute toxicity of cefuroxime axetil (CAM-AX), a cephalosporin derivative, was carried out using Sprague Dawley rats. CXM-AX was orally administered to the rat in doses of 0.125, 0.25, 0.5 and 1.0 g/kg/day for 5 weeks, followed by the recovery period of 4 weeks. Also, CXM-AX was compared with 1.0 g/kg/dav of cephalexin (CEX), a cephalosporinantibiotic.
In the CXM-AX treated groups, soft feces, transient diarrhea, increase in water consumtpion, cecal enlargement with increase in organ weight, and the retention of the test substance in the stomach were observed, whereas none of these changes were considered to be ascribable to the toxicity of CXM-AX.
In the group of 1.0 g/kg, decreases in serum glucose, triglyceride and totalprotein values, were observed. Histopathologically, focal degeneration of gastric mucosa was observed, while this finding was considered to be attributable to mechanical stimulation by residual solidtest substance in the stomach.
In the group of 0.5 g/kg, slight decreases in levels of serum glucose and total protein were observed.
In the groups of 0.25 and 0.125 g/kg, no toxicological findings were observed.
The above-mentioned changes disappeared after the 4 week-recovery period.
In the group of CEX 1.0 g/kg, changes were more evident than those in the same dosage group of CAM-AX in the above various examinations, though some of the changes remained even after the recovery period.
These results indicated that the maximum non-toxic dose level of CXM -AX was 0.25 g/kg/day in this subacute toxicity study in rats.

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A study on subacute toxicity of cefuroxime axetil tablet (CXM-AX tablet), a cephalosporin derivative, was carried out using Sprague Dawley rats. CXM-AX tablet was orally administered to the rat at doses of 0.125, 0.25, 0.5, 1.0 and 1.5 g/kg/day, as CXM-AX itself, for 5 weeks followed by the recovery period of 4 weeks.
In the CXM-AX tablet treated groups, soft feces, increase in water consumption, enlargement or weight increase of the cecum were observed, while none of these changes were thought to be due to the toxicity of CXM-AX tablet.
In the group of 1.5 g/kg/day, there were several rats which died or showed severe moribundity. These were considered to be attributable to mechanical stimulation of stomach by residual solid test substance in the stomach. In the other live rats, decreases in body weight gain, urinary potassium and cloride, and serum prOtein levels, and increase in serum GPT were observed.
In the groups of 1.0 and 0.5 g/kg/day, decrease in body weight gain, changes in hematological and biochemical test findings, changes in organ weights and slight damages to stomach were observed in a few animals.
In the groups of 0.25 and 0.125 g/kg/day, no toxicological findings were observed. These results indicated that the maximum non-toxic dose level of CXM-AX tablet was 0.25 g/kg as CXM-AX itself in this subacute toxicity study.
There were no essential differences in toxicity between CXM-AX and CXM-AX tablet.

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Acute and subacute oral toxicity studies on cefuroxime axetil (CXM-AX) were carried out in beagles.
a) In case of acute toxicity study, there was no death in any dogs examined. Changes induced by CXM-AX were vomiting, salivation, white-yellowish feces and slight decrease in food consumption. The results revealed that the lethal dose in beagles was higher than 5.0 g/kg.
b) In case of 5-week subacute toxicity study at doses of 0.25, 0.7 and 2.0 g kg day. there was no death of the test animals during the experimental period.
In the group of 0.7 g/kg or more, loose passage was observed mainly in the later part of the administration period. In haematological and bloodchemical examinations, decreases in haematocrit value, haemoglobin concentration, total cholesterol, phospholipid and total protein, and increases in A/G ratio and triglyceride were observed. In pathological observation, however, no changes attributable to the administration of CXM-AX were found.
The above-mentioned changes were not observed at the end of the 5-week recovery.
The non-effect dose level of CXM-AX in beagles was considered to be 0.25 g/kg/day in this study.

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Subacute toxicity study on cefuroxime axetil (CXM-AX) was carried out by 5-week oral administration at doses of 0.25, 0.7 and 2.0g/kg/day in 3-week-old beagles. The experimental results obtained are as follows:
There was no death in the test animals, and no abnormalities attributable to CXM-AX were observed in general clinical laboratory tests or pathological tests, excepting for a few accidental changes.
From the above-mentioned results, the non effect dose level of CXM-AX in juvenile beagles was considered to be 2.0g/kg/day in this 5-week subacute toxicity study.

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A study on chronic toxicity of cefuroxime axetil (CXM-AX), a cephalosporin derivative, was carried out using Sprague Dawley rats. CXM-AX was orally administered to the rat in doses of 30, 75, 200 and 500 mg/kg/day for 26 weeks, followed by recovery period of 13 weeks.
In the CXM-AX treated groups, soft feces, increase in water consumption, enlargement or weight increase of the cecum, decrease in serum gamma-globulin level and the residue of the test substance in the stomach were observed. But the above-mentioned changes were not thought to suggest toxicity of the drug.
In the group of 500 mg/kg, transient decrease in body weight, accompanying to soft feces or diarrhea, were observed during recovery period. Also, slight prolongation of prothrombin time, slight decreases in serum levels of lipids, total protein, and changes in several organ weights were observed.
Morphologically, mild change in gastric mucosa was observed at autopsy, but this was considered to be attributable to mechanical stimulation by solid test substance. No morphological other change in organs attributable to CXM-AX was observed in the pathological examination.
In the groups of 30, 75 and 200 mg/kg, no toxicological findings were observed.
These results indicated that the maximum non-toxic dose level of CXM-AX was 200mg/kg/day in this study.

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Teratological study on cefuroxime axetil (CXM-AX, SN 407), a newly developed cephalosporin antibiotic, was carried out in Sprague-Dawley rats. CXM-AX was administered orlly to female rats from day 7 to 17 of gestation at daily doses of 100, 300 and 1, 000mg/kg.
In dams, decrease in food consumption and increase in water consumption were observed in all dose groups. Also, increase in weight of cecum was observed in the autopsies on day 20 of gestation and on day 21 after delivery.
Observation of fetuses revealed no influence of CXM-AX on the number of implantations, the number of live fetuses, the incidence of embryonic death, body weight, body length, tail length, external forms, visceral organs, skeleton and degree of skeletal ossification.
In pups, no influence of CXM-AX were observed on live birth, viability and weanling indices, postnatal developments, body weight, external forms, visceral organs, skeleton, organ weights, sense, behavior, open field and avoidance response tests or reproductive performance.
Thus, in the present study, the maximum no-effect dose level of CXM-AX in dams was estimated to be about 100mg/kg, but even 1, 000mg/kg dose level was found to exert no effect on the reproduction of dams or the next generation.

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Fertility study on cefuroxime axetil (CXM-AX, SN 407), a newly developed cephalosporin antibiotic, was carried out in Sprague-Dawley rats. CX: M-AX was given by oral administration to the females for 14 days before mating, in the mating period and in the early stage of gestation (from day 0 to 7 of gestation) and to the males for 63 days before mating and in the mating period, at daily doses of 50, 150 and 500mg/kg.
In males, soft feces were found transiently (150mg/kg or more). Food consumption decreased in the early stage of administration (50mg/kg or more) and increased after day 22 of administration (150mg/kg or more). Increase in water consumption was found in the groups treated with 150mg/kg or more. However, there was no effect on body weight. No effect of CXM-AX was found in hematological examination in male rats. Serum biochemical examination revealed decrease in GOT and GPT levels (150mg/kg or more) which are common to other cephalosporin antibiotics. Increase in weight of cecum (150mg/kg or more) and the decrease in weights of the carcass (500mg/kg) were observed.
In females, soft feces were found transiently (50 mg/kg or more). Suppression of body weight gain was observed during gestation period (500mg/kg). Food consumption decreased in the early stage of administration (50mg/kg or more) and increased during gestation period (150mg/kg or more). Water consumption tended to increase (150mg/kg or more). Increase in weight of cecum (150mg/kg or more) was observed on day 20 of gestation.
No changes were observed in frequency of estrus, copulation index or fertility index.
Observation of fetuses revealed no influence on the number of corpora lutea, mortality of fertilized eggs before implantation, the number of implantations, incidence and stage of embryonic death and the number of live fetuses. No influences were also observed in sex ratio, developments of fetuses (body length, tail length, body weight, degree of skeletal ossification), external forms, visceral organs and skeleton.
Thus, it was inferred that CXM-AX had no influence on the reproductive performance in male and female rats, no lethal effect on fetuses in the early stage, no effect on implantation or development of fetuses in uterus. In the present study, the maximum no-effect dose level of CXM-AX in male and female rats was estimated to be about 50mg/kg, and that on the reproductive performance in male and female rats and their fetuses, to be 500mg/kg.

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Perinatal and postnatal study on cefuroxime axetil (CXM-AX, SN 407), a newly developed cephalosporin antibiotic, was carried out in Sprague-Dawley rats. CXM-AX was administered orally to female rats from day 17 of gestation through to day 20 after delivery at the daily doses of 100, 300 and 1, 000mg/kg.
3 dams in 1, 000 mg/kg dose group died of complication of perforative peritonitis on day 3 or 4 after delivery.
Transient soft feces were noted in 5 dams from day 2 to day 10 after delivery (1, 000mg/kg). Increase in body weight was observed from day 11 after delivery in every dose group. Transient decrease in food consumption at the early stage of administration and increase in water consumption from day 8 to day 9 after delivery were observed in every dose group. In necropsy performed on day 21 after delivery, increase in weight of the cecum was found in every dose group.
Observations of pups revealed no effect on live birth, viability and weanling indices. Suppression of body weight gain of pups was found on day 4, and day 7 after birth (1, 000mg/kg). Increase in weight of cecum was observed in males (300mg/kg or more) and in females (1, 000mg/kg) in necropsy on day 21 after birth. Increase in weight of cecum was observed in females (300mg/kg or more) at 12 weeks of age.
No influences of CXM-AX were observed in postnatal developments, external forms, visceral organs, skeleton, sense, behavior, open field and avoidance response tests or reproductive performance.
Thus, in the present study, the maximum no-effect dose level of CXM-AX in dams was estimated to be about 100mg/kg, and that on the reproduction of dams to be 300mg/kg and that on next generations to be 100mg/kg.

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Teratological study on cefuroxime axetil (CXM-AX, SN 407), a newly developed cephalosporin antibiotic, was carried out in New Zealand White rabbits. CXNI-AX was administered orally to female rabbits from day 6 to day 18 of gestation at daily doses of 7.5, 15 and 30mg/kg.
Four dams in 15mg/kg dose group and 8 dams in 30mg/kg dose group died. Food and water consumptions decreased in the live dams in 30mg/kg group.
In necropsy on day 29 of gestation, increase in weight of cecum at doses of 15mg/kg or more, and decreases in weights of the carcass and kidneys and increase in weight of thymus at dose of 30mg/kg were observed.
Decrease in fetal viability was observed in 15mg/kg group or more, and decrease in fetal body weight, body length and tail length were observed in 30mg/kg group.
There were no effects on the number of live fetuses, sex ratio, and incidence of embryonic death or anomaly.
Thus, in the present study, maximum no-effect dose level of CXM-AX on dams and fetuses was estimated to be 7.5mg/kg, and no teratological changes were detected in fetuses treated with CNM AX at dose of 30mg/kg.

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Effects of cefuroxime axetil (CXM-AX), a prodrug of cefuroxime, on rat and rabbit kidneys were investigated and compared with those of cephalexin (CEX) and cefroxadine (CXD). The results were as follows:
1. Effects on rat kidneys
(1) A single oral administration of 1.0g/kg of CXM-AX, CEX and CXD induced no toxicological change in kidneys. Also concurrent treatment with furosemide did not induced any toxicological finding in kidneys.
(2) No renal change was induced by 7-day administration of CXM-AX or CXD. However, functional and morphological changes in kidneys were induced by CEX.
(3) In combination with furosemide for 7 days, functional and morphological changes in kidneys were induced by CXM-AX and were slightly enhanced by CEX. However, no nephrotoxicity was induced by CXD combined with furosemide.
2. Effects on rabbit kidneys
A single oral administration of 0.5g/kg of CXM-AX, CXM-AX tablet, CEX or CXD induced no toxicological change in kidneys.

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Immunological properties (i. e. immunogenicity, cross reactivity and elicitogenicity) of cefuroxime axetil (CXM-AX, SN 407), an oral cephalosporin antibiotic, were compared with those of cefuroxime (CXM) and cephalexin (CEX). The results obtained were as follows:
1. Rabbits were immunised with emulsion of antibiotics and FCA (Freund's complete adjuvant), and it was found that IgM and IgG type antibodies against antibiotics were produced in them when antibodies were determined by the method of enzyme linked immunosorbent assay.
The activity of anti-CXM-AX sera was as high as that of anti-CXM sera, and higher than that of anti-CEX sera.
2. The immuno cross-reactivity with other β-lactam antibiotics was examined by indirect hapten hemagglutination inhibition test using rabbits' anti-CXM-AX sera. CXM-AX showed strong cross reactivity with CXM, and also showed weak cross reactivity with CET, ABPC and 7-ACA.
3. Mice were immunised with antibiotic-ASE (Ascaris suum extracts) conjugates, and it was found that IgE type antibodies were produced in them, which were reactive not only to antibiotic-HSA (human serum albumin) conjugate but also to antibiotics alone.
4. Active systemic anaphylaxis was tested in guinea pigs immunised with antibiotic-ASE conjugates. In the group sensitised with CXM-AX-ASE, no anaphylactic shock was caused in any case by challenge of CXM-AX alone. However, mild positive symptoms were evoked by intravenous challenge of CXM alone in a half of the cases. Challenge of CXM-AX-HSA and CXM-HSA conjugates caused fatal anaphylactic shock in all the cases within 5 mins.
5. Antigenicity of CXM-AX, when examined through immunisation by injection, was slightly stronger than that of CEX and comparable to that of CXM. From this, and the fact that CXM-AX is to be given orally in the clinical use, this drug is not considered to cause any severe allergic side effects compared with other cephalosporin antibiotics.

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General pharmacological properties of cefuroxime axetil (CXM-AX), a new cephalosporin antibiotic, were studied in experimental animals and the following results were obtained.
CXM-AX, given orally in the doses from 500 to 2, 000mg/kg, did not exert any effect on general behavior, spontaneous locomotion, motor coordination, response to pain, barbital-induced hypnosis, electroshock- or drug-induced convulsions, body temperature or conditioned avoidance response in mice or rats.Oral administration of CXM-AX did not affect spontaneous electroencephalogram in rabbits in the doses from 10 to 100mg/kg, or spinal reflex in cats in the doses from 300 to 1, 000mg/kg.
Blood pressure, heart rate, respiration and electrocardiogram were not influenced by oral administration of CXM-AX in the doses from 100 to 1, 000mg/kg in anesthetized dogs.CXM-AX at the concentration of 10^-4g/ml exerted no effect on motility of isolated atria of guinea pig whereas intraarterial injection of CXM-AX increased blood flow in hind limb in anesthetized dogs in the doses of not less than 10 mg/shot.Blood pressure response of anesthetized dogs and nictitating membrane contraction of anesthetized cats were not affected by oral administration of CXM-AX in the doses from 100 to 1, 000mg/kg.
CXM-AX at the concentration of 10^-4g/ml exerted no effect on spontaneous or drug-induced contractions in isolated ileum of rabbits or isolated ileum, trachea or was deferens of guinea pigs. Slight inhibitory effect of CXM-AX was observed, at the concentration of 10^-4g/ml, on drug-induced contractions in isolated rat uterus and isolated guinea pig aorta.Oral administration of CXM-AX in the doses from 500 to 2, 000mg/kg did not affect spontaneous motility of uterus in anesthetized rats. Although intestinal propulsion in mice was enhanced by CXM-AX in the dose of 2, 000 mg/kg, no effect on gastrointestinal motility in anesthetized rabbits was noted.
Gastric juice secretion in rats was decreased by intra-duodenal administration of CXM-AX in the dose of 1, 000mg/kg.In the oral doses of 250mg/kg or higher, CXM-AX decreased urinary excretion of Na ⁺ in rats, and, in the doses of 500mg/kg or higher, it decreased urinary volume.There was no local anesthetic effect, local irritation, anti-inflammatory effect or effect onneuromuscular junction of CXM-AX.
As described above, CXM-AX did not have effect on the central nervous system. Some effects on the cardiovascular system, peripheral nervous system and smooth muscles were observed only in very high doses of CXM-AX.

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High-performance liquid chromatography (HPLC) method for the quantitative determination was studied on cefuroxime (CXM), the parent drug of cefuroxime axetil (CXM-AX).Also, the stability of CXM in body fluids was examined.
CXM was well separated from other endogenous compounds which were present in body fluids. When 0.5-15μg/ml of CXM was added to human plasma, 10-1, 000μg/ml to human urine, 1-20μg/ml to rat serum, 10-150μg/ml to rat urine and 25-375μg/ml to rat bile, good calibration curves were obtained in all the cases.
The recoveries of CXM from serum and plasma were 85-87%, and those from urine and bile were 96-100%. The limit of detection was 0.2μg/ml for CXM both in human plasma and in rat serum.
CXM in body fluids was stable at least for two weeks if it was kept at -20°C or below.

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Absorption, distribition, metabolism and excretion of cefuroxime (CXM) were investigated in rats and dogs after single oral administration of 20mg/kg of cefuroxime axetil (CXM-AX, SN 407), and the following results were obtained.
1. After an oral dose of CXM-AX, the peak serum or plasma levels of CXM were 5.52μg/ml at 30 mins in rats and 10.09μg/ml at 60 mins in dogs. The serum and plasma half-lives were 70.2 and 73.8 mins, respectively.
2. The peak serum level of CXM in rats was, when compared with other drugs, as high as those of CEX and CCL, but lower than that of CFT. The peak plasma level of CXM was about a half of that of CEX in dogs.
3. The tissue levels of CXM in rats were the highest in kidney, and the second highest, in liver. The CXM levels in lung, heart and spleen were low.
4. The 0-24 hr urinary excretion rate was 30.3% in rats and 29.4% in dogs, and most of the urinary excretion took place within 6 hours. The 0-24 hr biliary excretion in rats was 1.60%.
5. After CXM-AX (20mg/kg/day) was given to rats by p. o. for 21 consecutive days, the CXM levels in serum and organs, and urinary excretion rate were similar to those after a single dose, and no drug accumulation was observed.
6. After CXM-AX was given to male and female rats, the peak serum level, serum half-life, AUC and urinary excretion rate in male rats were similar to those in female rats, with no difference between sexes.
7. After CXM-AX was given to rats in the fasting and non-fasting groups, the peak serum level, serum half-life, AUC and urinary excretion rate were comparable in these two groups, and no influence of feeding on pharmacokinetics was observed.
8. Active metabolite of CXM-AX was sought by bioautography. As a results, only CXM was detected in serum, plasma or urine.
9. The in vitro serum protein binding rates of CXM in mice, rats, rabbits, dogs and humans were 17 1, 37.1, 42.9, 19.6 and 35.0%, respectively. The in vivo serum protein binding rates, determined with serum of rats given CXM-AX, ranged 31.9-40.4% which was consistent with the in vitro study result on rats.

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Single and multiple doses of cefuroxime axetil (CXM-AX, SN 407), the prodrug of cefuroxime (CXM), was administered to 29 healthy male volunteers in Phase I clinical study to evaluate its safety, absorption and excretion.
1. The plasma and urinary levels of CXM after a single dose or multiple dose of 250mg or 500mg of CXM-AX given after meal were higher than those given in the fasting state.
2. Following single doses of CXM-AX 250mg, the mean plasma levels reached the peak at 2 hrs, and the mean peak levels were 3.74μg/ml when administered 30 mins after meal and 3.00μg/ml after administration in fasting. The plasma half life was 0.9 hr in both cases.
3. Following single doses of CXM-AX 500mg, the mean plasma levels reached the peak at 2-2.5 hrs, and the mean peak levels were 6.41μg/ml when administered 30 mins after meal and 4.64μg/ml after administration in fasting. Clear dose dependence was observed between 250 mg and 500mg dosing groups.
4. The 0-6 hr urinary recovery rates after single doses given 30 mins after meal and in the fasting state were 45-51% and 32-37%, respectively, whichever the dose was 250mg or 500mg.
5. When plasma concentrations and urinary recovery rates were compared between two 250mg tablets and one 500mg tablet, there was no difference.
6. After 46 multiple doses of CXM-AX 250mg three times daily, there was no tendency to accumulation. The concentrations of CXM or CXM-AX in faeces in this multiple dosing study was lower than the detectable limit. In plasma and urine, only CXM was detected and no other active metabolite was not detected.
7. In the drug tolerance study, transient, mild feeling of abdominal fulness was observed after multiple dosing, and slight elevation of GOT, GPT and Al-P values, after single and multiple dosing. However, no other abnormality attributable to the drug was noted in subjective and objective symptoms, physical examinations, haematology, serum-biochemistry or urinalysis.

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We carried out fundamental studies on cefuroxime axetil (CXM-AX, SN 407) to support its clinical use.
CXM-AX, a prodrug of cefuroxime (CXM), has broad antibacterial spectrum against Gram-positive, Gram-negative and anaerobic organisms. In our study, it demonstrated good antibacterial activities against S. aureus, S. e pidermidis, E. coli, K. pneumoniae, S. marcescens, C. freundii, P. mirabilis and B. fragilis isolated from patients with surgical infections, but not against P. aeruginosa.
After oral administration of CXM-AX, high serum level of CXM were obtained rapidly. Unlike conventional antibiotics, CXM-AX showed the properties of achieving higher serum levels following administration after meal than following administration in fasting. After administration of CXM-AX 250 mg in fasting, the serum levels reached the peak at 2 hrs, the mean peak levels being 3.0 μg/ml (bioassay) and 2.96 μg/ml (HPLC). Elimination half lives were 0.96 hr (bioassay) and 0.92 hr (HPLC), and the mean 0-8 hr urinary recovery rates were 36.0%(bioassay) and 35.4%(HPLC).
In the 500 mg dosing group, the mean peak serum levels of 4.37 μg/ml (bioassay) and 4.57 μg/ml (HPLC) were attained at 2 hrs after dosing, half lives being 0.95 hr (bioassay) and 0.92 hr (HPLC). The mean 0-8 hr urinary recovery rates were 28.5%(bioassay) and 27.(HPLC). These results indicate that CXM levels in serum correlate with the dose of CXM-AX.
In the metabolism study, no metabolite other than CXM was detected by HPLC determination of serum and urine. This proves that CXM-AX is excreted without being metabolised in body.

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Cefuroxime axetil (CXM-AX, SN 407) is a new oral cephem which exerts excellent antibacterial activity as cefuroxime (CXM) against Gram-positive, Gram-negative and anaerobic organisms after de-esterification taking place in the intestinal mucosa.
We have studied the levels of CXM in gallbladder tissues and the excretion into bile after oral administration of CXM-AX.
1) In 4 patients who had received 5 multiple doses of CXM-AX and cephalexin (CEX), at 500mg each, concurrently in 3 days, serum levels of CXM were 2.37μg/ml at 3 hrs and 2.13 & 0.34μg/ml at 4 hrs after the last dose and the gallbladder tissue levels were 1.02 & 0.23μg/g at 4 hrs. The corresponding gallbladder levels of CEX were 4.32 & 1.84μg/g.
2) When the excretion of CXM-AX and CEX into bile were compared up to 6 hrs after a single concurrent dose at 500mg each, the peak bile level of CXM was 8.64μg/ml, i. e. 6. 4 times higher than that of CEX which was only 1.34μg/ml. The 0-6 hr biliary recovery rates of CXM-AX and CEX were 0.063% and 0.021% of the given dose, respectively.
No subjective or objective symptoms of adverse effects such as rash or diarrhea were observed in any of these 5 patients.

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Fundamental studies on cefuroxime axetil (CXM-AX) were performed and the following results were obtained:
1) Antibacterial activity. CXM-AX had strong activities against S. epidermidis, E. coli, K. pneumoniae and P. mirabilis. The activities against P.vzilgaris, M. morganii, Citrobacter and Enterobacter were moderate but superior to those of other drugs examined.
2) Absorption and excretion. The peak plasma levels of CXM-AX and CCL in five healthy subjects were observed at 3 hrs after the administration, showing 2.77±0.51 μg/ml for CXM-AX and 2.33± 0.77 μg/ml for CCL. The half lives of them were 1.62 hrs and 2.04 hrs, respectively. The cumulative urinary recovery rate within the first 8 hrs was 55.3% for CXM-AX and 72.6% for CCL. On the other hand, the half life of CXM-AX was prolonged in the patients with impared renal function.
3) Antibacterial activities in the urine. The bacteriocidal concentration of CXM-AX was very similar to its bacteriostatic concentration. Consequently, the activity of CXM-AX and CCL in the urine was on a par, although the excreted concentration of CCL was higher than that of CXM-AX.
4) Concentration in the prostate. The ratio of prostatic level to serum level was 0.37±0.17 at 2 hrs after the administration at the dosage of 500 mg of CXM-AX.

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Cefuroxime axcetil (CXM-AX), an orally absorbed pro-drug of cefuroxime (CXM), was studied. The MICs of CXM were determined for 137 clinical isolates of 6 species, using plate dilution method with inoculum size of 10⁶ cfu/ml. The MICs of CXM ranged 0.39->100 μg/ml for S. aureus, 3.13-12.5 μg/ml for E. coli, 1.56-25 μg/ml for K. pneumoniae, 1.56-100 μg/ml for P.mirabilis, 12.5-50 μg/ml for M. morganii, 6. 25->100 μg/ml for Serratia spp.
CXM-AX was administered orally in a dose of 250 mg to 6 healthy male volunteers in the fasting state and after meal using crossover manner. There were differences between the pharmacokinetics of CXM-AX in the fasting state and that after meal.
When CXM-AX was dosed in the fasting state and after meal, T_max was 1.4 and 2.8 hours, C_max was 2.9 and 3.2 μg/ml, T 1/2 was 1.1 and 1.6 hours and AUC was 9.0 and 15 μg·hr/ml, respectively. The 0-6 hour urinary excretion rate of CXM-AX was 23.4% after doses in the fasting state and 43.6% after meal.
The absorption of CXM-AX was significantly better when the drug was given after meal than when it was given in the fasting.
It is recommended that patients should take doses of CXM-AX shortly after meal. Twenty nine patients, including 20 with respiratory tract infections and 9 with urinary tract infections were treated with CXM-AX for 3-10 days, mainly in the dose of 250 mg t. i. d.
Clinical effect was excellent in 10 cases, good in 14 cases, fair in 3 cases and poor in 2 cases. The efficacy rate was 83%.
The only side effect noted was diarrhea which occured in one case.

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Cefuroxime axetil (CXM-AX), an oral Cephalosporin, is the 1-acetoxyethyl ester of Cefuroxime (CXM) which is practically not absorbed by the oral administration. CXM-AX itself does not exert antibacterial activity. But when orally administered, it is absorbed in the gastrointestinal tract through de-esterification, to exert antibacterial activities as CXM.
CXM-AX was given to a total of 10 patients with respiratory tract infections in the daily dose of 750 mg, to evaluate its clinical efficacy, safety and usefulness.
In 10 patients (6 with pneumonia and 4 with chronic bronchitis), clinical efficacy was good in 7 patients (5 with pneumonia and 2 with chronic bronchitis) and fair in 3 patients (1 with pneumonia and 2 with chronic bronchitis), the efficacy rate being 70. 0%.
Neither adverse events nor abnormal laboratory findings were noted in any patient.
These results indicate that CXM-AX is a reliable, antibiotic agent with interesting features.

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To evaluate the clinical efficacy of cefuroxime axetil (CXM-AX), the treatment was made with the drug in 9 patients including 6 with acute bronchitis, 1 with acute exacerbation of chronic bronchitis, 1 with chronic pyelitis and 1 with chronic cystitis. Responses were good in 8 patients and poor in 1. The efficacy rate of cefuroxime axetil was 88.8%. All of the 4 strains isolated from patients as causative organism were eradicated after administration, although superinfection was observed in one case.
No side effect or abnormal laboratory finding due to the treatment with the drug was observed.

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The therapeutic effects of cefuroxime axetil (CXM-AX), an ester derivative of cefuroxime, which was developed in the United Kingdom as a new oral cephem, on respiratory and urinary tract infections were evaluated. A daily dose of 750-1500 milligrams of cefuroxime axetil was given to a total of 56 cases consisting of three patients with acute tonsillitis, 14 patients with acute pharyngitis, 18 patients with acute bronchitis, 10 patients with chronic respiratory tract infections, seven patients with acute pneumonia and four patients with acute cystitis. The clinical effects were excellent in six patients, good in 36, fair in four and poor in six patients with respiratory infections, and excellent in all of the four patients with urinary tract infections. In respiratory infections, a total of 19 microbes which consisted of six strains of H. influenzae, three strains each of S. aureus and S. pneumoniae, two strains of E. faecalis and one strain each of S. epidermidis, K. oxytoca, Pseudomonas sp., Acinetobacter sp. and unidentified GNB were identified as causative organisms. But two of them were excluded from bacteriological evaluation. Fourteen of the remaining 17 strains were eradicated by treatment with cefuroxime axetil. As regards urinary tract infections, four strains of E. coli were identified as causative organisms. All of them were eradicated by treatment with cefuroxime axetil. No side effect whatsoever was observed. An elevation of values of the activity of enzymes released from the liver was observed in three patients, and eosinophilia, in one patient. These changes return ed to normal after completion of therapy with cefuroxime axetil.
From the above results, it was concluded that cefuroxime axetil is one of the most useful antibiotics for oral use in the treatment of outpatients with upper and lower respiratory infections.

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Clinical evaluation of Cefuroxime axetil (CXM-AX) was performed in 18 patient s with RTI. They consisted of nine males and nine females aged from 17 to 71 years old, 16 of whom suffered from acute exacerbation of chronic RTI, one D. P. B. and one pneumonia.
CXM-AX was given orally to 14 patients in daily dose of 750 mg in three divided portions and tofour patients in daily dose of 1, 000 mg in four divided portions. The durations of administration were seven days in 15 patients, 14 days in two patients and four days in one.
A total of six strains, comprising H. influenzae three strains, S. aureus two strains and S. pneumoniae one strain, were identified from the sputum before administration. Five strains were eradicated but one strain of H. influenzae was not eradicated after seven days, administration.(eradication ratio=83. 3%)
The clinical efficacy rate was 94. 4%(17/18); Excellent in two cases, Good in 15 cases and Fair in one case.
There were no side effects and abnormal findings in laboratory test values in any of the patients.
From the above results, it is concluded that CXM-AX is an effective, safe and useful new cephem.

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Cefuroxime axetil was orally administered at a dose of 500 mg or 250 mg three times a day after meal to ten patients with pulmonary or urinary tract infections. Clinical responsewas ‘good’ in two patients and ‘fair’ in one patient with pneumonia and ‘good’ in all the cases of urinary tract infections, i. e., three cases of pyelonephritis and four cases of cystitis and asymptomatic bacteriuria. As to causative organisms of urinary tract infections, five strains of E. coli and one strain each of K. pneumoniae and P.mirabilis were all eradicated, but one strain of P. aeruginosa combined with P. mirabilis persisted.
No clinical side effect was observed. As abnormality in laboratory findings, elevation of GOT and GPT was observed in one case, and elevation of GOT, GPT and Al-P in another case.

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A new oral cephem antibiotic, cefuroxime axetil (CXM-AX) was administered to total 28 patients consisting of 26 with respiratory tract infections and 2 with urinary tract infections, and its efficacy and safety were studied. The study was carried out from September, 1984 to May, 1985. The patients consisted of 11 adult males and 17 adult females in this study. The mean age of the total patients was 57.5 years (range: 18-80).
CXM-AX was given three times a day at a dose of 250 mg or 500 mg in the patients with respiratory tract infections and at a dose of 250 mg in the patients with urinary tract infections. The duration of therapy ranged from 3 to 14 days, the total dose ranged from 2.25 to 21.0 g.
The therapeutic effect was ‘ Excellent ’ in 1 patient, ‘ Good ’ in 18, ‘Fair’ in2, ‘Poor’ in 3, ‘ undetermined ’ in 4, with a high effectiveness rate of 79.2%. As an adverse event, diarrhea was observed in one patient. Laboratory tests revealed decrease in neutrophil in one case. however, these symptom and finding were mild and no severe side effects caused by the drug were observed.

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In this paper, the author reports the results of clinical investigation on CXM-AM. Evaluation was made for the clinical efficacy and safety of the drug in 18 patients with respiratory tract infections, i. e. 3 with tonsillitis, 5 with acute bronchitis, 6 with acute exacerbation of chronic bronchitis, 2 with bronchiectasis and 2 with pneumonia. The clinical response was good in 14 cases, fair in 3 and poor in 1, the clinical efficacy rate being 77.7%.
As to the adverse event, rash was observed in 1 case, which, however, disappeared within 5 days following discontinuance of administration. There was no abnormal finding noted in the laboratory examination.

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The in-vitro and clinical studies were performed on Cefuroxime axetil (CXM-AX), a newly developed cephem antibiotic, 1-acetoxyethyl ester of Cefuroxime (CXM) for oral use.
The MICs of CXM for 190 strains of 10 species of clinical isolates were compared with those of other antibiotic agents (Cephalexin (CEX), Cefaclor (CCL), Cefadroxil (CDX) and Ampicillin (ABPC)). The antibacterial activity of CXM against S. aureus was superior to that of any other antibiotic, and that against S. pneumoniae was comparable to that of ABPC and higher than those of other antibiotics studied.
In the clinical study, CXM-AX was administered to a total of 11 patients, namely 7 with respiratory tract infections (pneumonia: 4, bronchiectasis: 1, upper respiratory tract infections: 1, mycoplasmal pneumonia: 1) and 4 with urinary tract infections, in the daily dose of 1, 500 mg for 5-19 days.
The clinical response was Excellent in 6, Good in 1, Fair in 2 and Poor in 1, and the other case (mycoplasmal pneumonia) was excluded.
No adverse event was developed in any patient. As for abnormal laboratory findings, transient elevation of transaminase values was observed in 2 cases, both of which were only mild ones.

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Clinical studies were performed on Cefuroxime axetil (CXM-AX), a newly developed cephalosporin antibiotic.
Nine patients consisting of 5 patients with acute bronchitis, 2 with acute tonsillitis, one with acute cystitis and one with F. U. O. were treated with CXM-AX in daily oral doses of 750mg for 6-10 days. Clinical effect was excellent in 2 patients, good in 6 and poor in one. The efficacy rate was 88%.
No side effect was observed, but slight elevation of s-GOT and s-GPT was observed in one patient.

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Effect of simulated oral administration of 250mg of cefuroxime axetil was determined on the viable counts of the S. aureus and the E. coli. By exposure of the S. aureus with MIC of0.78μg/ml to the fluctuating levels of cefuroxime axetil which would occur in vivo, 99.9% eradication of the inoculum of bacteria was observed at 6 hr. after inoculation and regrowth did not resume at 8 hr. Exposure of the E. coli strain with MIC of 0.2μg/ml resulted 99.999% eradication of the inoculum of bacteria at 6 hr. after inoculation. The E. coli strain with higher MIC of 6.25μg/ml decreased by 2 log₁₀ below the counts of inoculum at 3 hr. followed sharply by logarithmic growth.
Cefuroxime axetil was administered to seven patients. Two patients with respiratory tract infection, two with acute pyelonephritis, and one with cholecystitis responded satisfactorily. Two patients with chronic cystitis failed to respond. No adverse effect was observed.

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Cefuroxime axetil (CXM-AX) was used in 9 patients with broncho-pulmonary infections.
Clinical effects were assessed as excellent in 1 case, good in 5 cases and poor in 3 cases.
Causative organisms were S. aureus (1 case), H. influenzae (1 case) and K. pneumoniae (1 case). After CXM-AX treatment, S. aureus and H. influenzae were eradicated and K. pneumoniae were decreased.
No evidence of side effect or abnormality in laboratory data was detected.

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The fundamental and clinical studies were performed on Cefuroxime axetil (CXM-AX, SN 407), a newly developed oral cephalosporin.
After a single oral dose of 500mg of CXM-AX in two healthy male volunteers in the fasting state, the blood levels of CXM were 3.12 and 4.17μg/ml respectively at one hour, and reached the peaks of 3.87 and 5.59μg/ml at 1.5-2 hours. The serum half-lives (T1/2) were 1.89 and 1.23 hours, respectively. The 0-6 hr urinary recovery rates were 40.7% and 17.0%.
Clinical efficacy of CXM-AX was evaluated in 4 cases, i.e.3 of acute bronchitis and 1 of acute cystitis. The causative organism was E. coli in the acute cystitis case, but was not isolated from the acute bronchitis cases. CXM-AX was administered in the dose levels of 250mg twice or three times daily. The clinical efficacy was good in all the cases.
No noteworthy adverse events or abnormal laboratory findings were noted.

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Cefuroxime axetil (CXM-AX) was administered to 7 cases (Acute bronchitis 3 cases, Bronchopneumonia 3 cases, Acute cystitis 1 case). This medication was given by per os at a daily dose of 250mg or 500mg t. i. d. for 7-15 days. The clinical efficacy was good in 3 cases, fair in 3 cases and poor in 1 case. Bacteriologically, the elimination of one strain each of S. aureus and H. influenzae was observed.
No clinical side effects nor abnormal laboratory findings were observed in this study.

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Cefuroxime axetil (CXM-AX), a newly developed prodrug of cefuroxime, was studied for its clinical efficacy. CXM-AX was used in the treatment of 10 cases of respiratory infectious diseases comprising 3 cases of chronic bronchitis, 3 cases of diffuse panbronchiolitis, 2 cases of bronchiectasis with infection, one case of acute pneumonia and one case of pulmonary emphysema with infection.
CXM-AX was administered orally at a dose of 750-1, 500mg, 3 times daily for 7-18 days and results obtained were good in 6 cases, fair in 2 cases and poor in 2 cases, the efficacy rate thus being 60%.
As for bacteriological effect, H. influenzae persisted in all the 4 cases but B. catarrhalis was eradicated in one case.
Adverse reaction such as drug eruption, drug fever, nausea, vomiting, diarrhoea were not observed and as for the laboratory findings, transient slight elevation of serum creatinine was found in one case.

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We studied the clinical efficacy of Cefuroxime axetil (CXM-AX), a new oral cephalosporin, in forty patients with bacterial respiratory tract infections.
The results obtained were as follows:
1) Cefuroxime axetil was effective in two out of three cases with acute pneumonia (efficacy rate: 66.7%), and was also effective in 28 out of 37 cases with lower respiratory tract infections (efficacy rate: 75.7%).
2) All the cases with Staphylococcus sp., Staphylococcus aureus and Streptococcus pneumoniae, each one case, showed good response to the treatment with Cefuroxime axetil. Seventeen out of 20 cases with Haemophilus influenzae also showed good response (efficacy rate: 85%). On the other hand, the efficacy rate in other Gram-negative rods was not so good: 25% in Escherichia coli, 50% in Klebsiella pneumoniae and Proteus mirabilis, 0% in Enterobacter aerogenes and Pseudomonas aeruginosa and 33. 3% in glucose non-fermentative Gram-negative rod, respectively.
3) There was no significant difference in the clinical effectiveness of Cefuroxime axetil between the two groups with a daily dose of 0.75 g and 15g.
4) As a side effect, diarrhea was observed in one case. And two cases showed mild eosinophilia after the treatment with Cefuroxime axetil.
In conclusion, Cefuroxime axetil is an effective and safe drug for treatment of respiratory tract infections.

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Cefuroxime axetil (CXM-AX), a prodrug of Cefuroxime (CXM), was studied for its absorption and excretion and clinical efficacy, and following results were obtained.
1. Blood levels and urinary excretion
Following a single oral dose of CXM-AX 250mg (CXM equivalent), given 30 mins after breakfast, the blood levels of CXM in 5 healthy male volunteers reached the peak of 3.12μg/ml at 2 hrs, and then declined gradually to less than 0.49μg/ml at 6 hrs, with the mean serum half-life of 1.07 hrs.
When the blood level profile of CXM was compared with that of Cefaclor in the equal dose, peak blood level and AUC of CXM were significantly higher. 0-6 hr cumulative urinary recovery rates of CXM and Cefaclor were 51.6% and 65.6%, respectively.
When probenecid was used concurrently for the investigation of the effects of probenecid on blood levels and urinary excretion, peak blood level and AUC became higher, serum half-life was prolonged and 0-6 hr cumulative urinary recovery rate decreased, with statistically significant difference. This suggested that CXM-AX had the mechanism of renal tubular excretion in man.
2. Clinical results
CXM-AX was administered to 7 patients with infections in the internal medicine, in the daily dose of 750mg for 4-7 days. The clinical response was good in 4 cases and poor in 3 cases. Bacteriologically, all strains of B Group Streptococcus, H. influenzae, E. coli and P. rettgeri, i. e. all the organisms other than P. aeruginosa were eradicated.
No side effect or abnormal laboratory value was observed in any patient.

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Cefuroxime axetil (CXM-AX) is a new oral cephalosporin antibiotic developed by Glaxo UK. We treated 2 patients with upper respiratory tract infections, 26 patients with lower respiratory tract infections and 1 patient with urinary tract infection with CXM-AX to evaluate its clinical effects and safety, and herewith report the results.
CXM-AX was administered orally in the daily dose of 750-1, 500 mg in 2 or 3 divided doses. The duration of treatment ranged from 3 to 21 days and the total dose, from 3 to 21 g.
The clinical effects were good in both of the 2 cases of upper respiratory tract infections, 20 out of 26 cases of lower respiratory tract infections and 1 case of cystitis. The efficacy rate (proportion of excellent and good cases) in a total of 29 cases was 79%.
Bacteriological response was evaluable in 12 cases. In all of the cases, one each with S. pneumoniac, S. agalactiae, Streptococcus sp., K. pneumoniae and K. oxytoca, eradication of strains was achieved. Out of 3 cases of H. influenzae, strains were eradicated in 2 and persisted in 1. In contrast, out of 3 cases of E. coli, strains were eradicated in 1 and persisted in 2.
As for side effect, diarrhea was observed in 1 case. Abnormal changes in laboratory data were noted in 3 cases, i. e. elevation of GOT and GPT in 2 cases and elevation of GOT, GPT and Al-p in 1 case, but these were all only slight changes.
The above results suggest that CXM-AX is a drug which can be used effectively and safely.

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Cefuroxime axetil (CXM-AX), a new orally absorbed prodrug of cefuroxime, was studied for its clinical efficacy in 3 cases of acute upper respiratory tract infections, 2 cases of pneumonia, 3 cases of chronic bronchitis and 3 cases of bronchiectasis.
The therapeutic responses were excellent in 2 cases, good in 3 cases, fair in 2 cases and poor in 4 cases.
The rate of efficacy was approximately 45%.
As for adverse events associated with the drug, one case of diarrhea and one case of dizziness were noted (18% of total cases).
This relatively low efficacy rate was due to strains of P. aeruginosa isolated as causative organisms in 3 cases in this study.
But S. aureus, S. pyogenes, β-hemolytic st. and K. pneumoniae were all eradicated.
The above results suggest the usefulness of this drug for the treatment of community acquired respiratory tract infections.

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Cefuroxime axetil (CXM-AX), a new orally-absorbed prodrug of cefuroxime, was evaluated clinically in 14 patients aged 19-62 years with respiratory tract infections (10 cases) and urinary trac infections (4 cases). A daily dose of CXM-AX was 750 mg in three divided oral doses, and the duration of CXM-AX therapy ranged from 5 to 14 days.
The results were as follows.
1. The clinical response to CXM-AX therapy of respiratory tract infections was good in 8 cases, poor in one and unknown in the other (mycoplasma pneumonia), and that in urinary tract infections was excellent in one case and good in 3 cases. The overall efficacy rate was 92%.
2. No side effect was noted.

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Cefuroxime axetil (CXM-AX) was administered to ten patients with a variety of infectious diseases.
All patients responded well. All of the three isolated strains of S. pneumoniae were eradicated. No adverse effect was observed clinically. Eosinophilia was found in two cases and leukopenia appeared in one.

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CXM-AX was administered to a total of 15 patients, i. e. 2 with acute upper airwayinfections, 5, with acute bronchitis, 1 with pneumonia, 1 with bronchial asthma, 1 with bronchiectasis, 4 with chronic bronchitis and 1 with acute enteritis.
The following results were obtained.
1. Clinical response was “Excellent” in 4 cases, “Good” in 9 and “Poor” in 2, the efficacy rate being 86.6%(13/15).
2. In 7 cases in which causative organisms were identified, bacteriological response was “Eradicated” in 4, “Decreased” in 1 and “Unknown” in 2.
3. As for side effects, itching and soft stool were observed in one case each. Both of them, however, were only mild and administration was continued.
4. No abnormal laboratory findings were noted.
5. The serum levels of CXM were attained at 1-2 hrs after oral dosing of 250 mg or 500 mg of CXM-AX after meal, and the serum levels were not in proportion to the doses given.
6. Usefulness of CXM-AX is evident, particularly in its nature that it exerts effects even in the treatment of out-patients including those with chronic respiratory infections.

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Cefuroxime axetil (CXM-AX), a new oral cephem antibiotic, was evaluated for its antibacterial activities, absorption and clinical effectiveness. The following results were obtained.
1) Antibacterial activities: MICs₈₀ of CXM-AX for 25 strains each of clinically isolated S. aureus, E. coli, K. pneumoniae, P. mirabilis and E. cloacae were 1.56, 25, 3.13, 25 and 50μg/ml, respectively, the value for S. aureus being the lowest.
2) Absorption: Following oral administration of CXM-AX in the dose of 500 mg (250mg tablet×2) to 3 patients with normal renal functions after meal, the blood levels were 0.56-4.24μg/ml (mean: 2.67μg/ml) at 2 hours after dosing.
3) Clinical results: CXM-AX was administered to a total of 28 patients, i. e. 2 with bacterial pneumonia, 12 with acute bronchitis, 6 with chronic bronchitis, 1 with acute pharyngitis, 4 with acute cystitis, 1 each with chronic cystitis, acute pyelonephritis and chronic pyelonephritis, in the dose of 250-500 mg bid. or. tid. Clinical efficacy was assessed as good in all the cases of bacteria pneumonia, acute pharyngitis, acute pyelonephritis and chronic pyelonephritis, 9 out of 12 cases of acute bronchitis and 3 out of 4 cases of acute cystitis. No adverse event attributable to the drug was, observed.

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Cefuroxime axetil (CXM-AX, SN 407), a newly developed oral cephalosporin antibiotic, was used in 12 patients with respiratory tract infections and one patient with infectious mononucleosis. The daily dose of 750-1500 mg was given in 3 divided doses after meals for 6-12 days. The diagnosis consisted of bronchiectasis in 8 cases and middle lobe syndrome, chronic bronchitis, bronchial asthma with infection, acute upper respiratory infections and infectious mononucleosis in 1 case each.
Clinical effects were excellent in 1 (9.1%), good in 8, fair in 2 and unknown in 2. The efficacy rate was 81.8%.
No clinical side effect was observed. In laboratory data, increase in eosinophil was noted in 1 patient. But it is not considered that this is attributable to the drug, because in this patient complicated with bronchial asthma, increase in eosinophil had been noted several times, irrespective of administration of antibiotics.

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