Antibacterial spectrum and antibacterial activity of cephradine are similar to those of cephalexin, sensitivity distribution is almost the same among clinically isolated Staphylococcus and Escherichia coli, and correlation was noticed between two drugs. Influence of medium pFI, human serum protein and inoculum size on in vitro antibacterial activity showed the same tendency to cephalexin. As for the stability of β-lactamase, the drug was stable to PCase, while inactivated to CEPase. As for the type of antibacterial action, difference depended on species. In the case of Staphylococcus, bactericidal action was observed at the level of MIC, while in the case of Escherichia coli, bacteriostatic action was recognized at the level near MIC. About the treatment effect of the drug for experimental infection of mice, the result exhibited to be similar to that of cephalexin.
From the above results, in comparison between cephradine and cephalexin no difference was observed be. tween two drugs in both in vitro antibacterial activity and in vivo antibacterial activity.

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Antibacterial activity of cephradine was compared in in vitro and in vivo with that of cephalexin
Antimicrobial spectrum, influence of medium pH, serum protein binding, MBC/MIC ratio and susceptibility of clinical isolates with cephradine were all quite similar to those with cephalexin.
Cephradine was well absorbed, distributed into various organs, and highly excreted into urine in mice by oral administration equally by subcutaneous administration as was in the case of cephalexin.
Cephradine was equally effective to cephalexin in protecting various bacterial infections in mice.

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The pharmacological actions of cephradine (CED) were investigated and compared with those of its related compounds.
The actions and minimal effective doses (MED) of cephradine were summarized as follows : inhibition on the excised heart of the guinea pig (10^-3 g/ml), bradycardia on ECG of the rabbit (100 mg/kg), dilation on the excised ear vessel of the rabbit (5×10^-2 g/ml), stimulation on the permeability of abdominal skin vessel of rabbit (1, 000 μg), inhibition on the excised tracheal muscle of the guinea pig (2×10^-3 g/ml) and inhibition on the excised non-pregnant and pregnant uterus of the rat in concentrations of 2×10^-3 g/ml and 2×10^-4g/ml respectively.
Its actions were similar to those of cephalexin and MED were larger in general.
These MED also were much larger than minimum inhibitory concentrations and maximum blood levels i clinical uses.
Therefore, it is concluded that cephradine is one of the antibiotics which have less pharmacological actions.

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Central actions of cephradine were investigated.
1. Cephradine did not enhance an ether anesthesia and a pentobarbital sleep at doses up to 200mg/kg s. c. in mice.
2. Cephradine did not protect against supramaximal electroshock and pentetrazol convulsions at doses up to 200mg/kg i. p.
3. No analgesic effect, nor ataxic or muscle-relaxant action was observed in mice injected cephradine at doses up to 200mg/kg s. c.
4. Cephradine did not influence on rabbit temperature at doses up to 200mg/kg p. o. or i. v.
5. Spontaneous motor activity in mice was not decreased by cephradine at doses up to 300mg/kg p. o. or i. v.
6. No emetic nor antiemetic effect of cephradine was observed at doses up to 100mg/kg p. o. or i. v.
7. Cephradine did not influence on EEG in rats and cats at doses up to 300mg/kg i. v.
Therefore, it is concluded that cephradine has no marked central actions at a clinical dose.

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Acute toxicity of cephradine was studied in mice and rats by oral, subcutaneous, intraperitoneal and intravenous dosing, subacute toxicity for 13 weeks and chronic toxicity for 26 weeks in rats by oral dosing, and subacute toxicity for 13 weeks in dogs by intravenous dosing.
LD₅₀ values (mg/kg) obtained were as follows : (male, female) in mice; po 3, 936, 3, 549, iv 4, 571, 4, 656 and in rats; po> 12, 000, > 12, 000, iv >2, 500, >2, 500.
Maximal no effect dose in both subacute and chronic oral toxicity studies in rats was 500 mg/kg/day, and in intravenous subacute toxicity study in dogs any toxicological sings and findings were not revealed even at the highest dose of 400 mg/kg/day.
Though a slight toxicity to renal tubles was found by successively oral dosing of more than 1, 000 mg/kg/ day in rats, any effect attributable to cephradine was not observed in whole body.
In mice and rats teratogenecity of cephradine by oral dosing to fetuses and their postnatal development were studied, and any abnormality was noted.

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1. Silicon coatingしたKieselgelプレートを用いてCephradineとCephalexinを分離, 定量する紫外分光光度法 (UV法) および混合試料中の両薬物の存在比を直接測定できる核磁気共鳴吸収スペクトル法 (NMR法) を併用して, 投与ラット尿中のCephradineとCephalexinを定量した。
2. 測定用試料はAmberlite XAD-2 resinカラムを使用して, または, さらにKieselgel F 254プレート上のPreparative TLCを併用して精製した。
3. その結果, Cephradine水溶液を50mg/kgで経口投与した絶食ラットの0～6時間ならびに6～24時間尿中には, それぞれ投与量の73%および9.22%のCephradine (+Cephalexin) が検出された。0～6時間尿に回収されたCephradine中のCephalexin含量はUV法で4.71～5.40%, NMR法で6.1～6.5%であった。6～24時間尿はNMR法で4.4%を示した。Cephradine原体は, もともと3.26 (UV法) ～3.7% (NMR法) のCephalexinを含むものを使用しているので,,回収Cephradine中のCephalexin含量はわずかに2～3%増加しているに過ぎない。この程度の変化は試料調製途上での可能性を否定できない。
結論として, ラットに投与されたCephradineは体内では, ほとんど代謝を受けることなく, 尿中に速やかに排泄されるといえる

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Cephradine concentrations in serum, bile and urine of dogs with bile-fistula were determined by bioassay after oral or intraduodenal administration.
Cephradine absorbed from gastro-intestinal tract was rapidly concentrated into liver bile corresponding to the serum level, the concentration ratios of bile to serum being 4. 2 to 14 during 2 to 24 hours after oral administration. This feature in biliary excretion of cephradine appears to be the same as in cephalexin conferring about the values in literature.

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Cephradine, a new cephalosporin, has an antibacterial activity of a broad spectrum similar to that of cephalexin.
The authors have measured the concentrations of the drug in oral tissues such as gingiva, tongue, pulp, submaxillary lymphonodi, submaxillary glands and parotid glands using Wistar strain rats, after 100 mg of cephradine were administered orally. The measuring method employed was a thin layer cup method using Sarcina lutea PCI 1001 as the test organism. The results were obtained as follows.
1) The concentration of cephradine reached to the maximum level rapidly as in half an hour.
2) The concentration of all the oral tissues was lower than that of serum.
3) Though cephradine was administered orally, the concentrations in serum and tissues were almost the same as those with other cephalosporins injected.
4) Little difference was noticed between concentration patterns of cephradine and cephalexin.

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Laboratory and clinical studies were carried out on cephradine, a new semisynthetic cephalosporin derivative, and the following results were obtained.
1) Sensitivity test wes performed with cephradine by a plate dilution method on 23 strains of Staph. aureus, 14 of E. coli, 4 of Klebsiella and 5 of Ps. aeruginosa, and the results obtained were similar to those of cephalexin. Cross resistance between two drugs was found in regard to Staph. aureus.
2) Oral absorption and excretion were investigated with cephradine in human subjects. Peak serum level of 16.6 pg/ml was obtained 1 hour after a 500 mg single close, and 57% of a close administered was excreted within 6 hours.
3) Protein binding was studied using cellophane bag dialysis, and a low binding rate was found with monitrol 1 plasma.
4) Thirty cases with bacterial infections, including 4 cases of pneumonia and 4 cases of acute cholecystitis, were treated by oral administration of cephradine, and 27 cases responded to the treatment, while 3 failed. During the treatment, 2 patients complained of gastro-intestinal disturbances, though the cessation of the antibiotic was not required. Two patients showed leucopenia, and another 1 case high transaminase level.Nevertheless, no serious side effect was encountered with the treatment.

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Laboratory and clinical studies of cephradine were performed with following results.
1) Susceptibility :
Cephradine showed MIC values of 12.5-> 100μg/ml against 25 strains of Klebsiella isolated from sputa. The distribution of MIC of cephradine against Klebsiella was almost equal to that of cephalexin.
2) Tissue distribution in rats :
After intramuscular administration of cephradine 50mg/kg, the peak levels were measured in kidney, liver, blood and lung in order. They attained the peak at 15 minutes in all tissues.
3) Serum levels after oral administration in men :
There was a tendency that peak levels after preprandial administration were higher than after postprandial administration.
4) Cliniacl aplication :
Cephradine was administered orally to 21 patients (respiratory infection 11 cases, urinary infection 9 cases, liver abscess 1 case) at a daily dose of 1.5-3.0g. Cephradine was remarkably or moderately effective in 17 of 21 patients.
5) Adverse reactions :
Some side effects were observed in 4 cases; diarrhea in 2 cases, exanthema in one case and mild elevation of serum GOT and GPT in an another case. The two patients suffering from diarrhea were improved, however in spite of consecutive administration of cephradine. And the others were restored to normal by cessation of administration.

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Cephradine was administered, orally to 14 patients. The results obtained were as follows : Effective in all 3 cases of acute tonsillitis, effective in 3 cases and slightly effective in 2 cases among 5 cases of pneumonia, and effective in all 6 cases of urinary tract infection due to E. coll. No subjective side-effect was noticed with cephradine. A case presented eosinophilia of around 10% during cephradine therapy, and the count reduced after completion of cephradine treatment.

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1) Antibaecterial activities of cephradine and cephalexin were investigated in vitro against Gram-negative bacilli. Minimum inhibitory concentrations of cephradine against the strains of E. coli, Klebsiella and Proteus mirabilis were generally two-fold higher than those of cephalexin. No significant difference was detected however between minimum bactericidal concentrations of cephradine and those of cephalexin against the strains of E. coli. Lower minimum bactericidal concentrations were observed more in the strains of Proteus mirabilis with cephradine than with cephalexin. Minimum bactericidal concentrations paralleled well with minimum inhibitory concentrations against the strains of Klebsiella with both cephradine and cephalexin.
2) Cephradine was administered clinically at a daily dose of 1 to 2 g for 14 to 40 days in 5 cases of acute pyelonephritis and 5 cases of chronic pyelonephritis. E. coli was causative in all the cases, and the sensitivity to cephradine was excellent except 1 case of chronic pyelonephritis. Cephradine was effective in all the cases of acute pyelonephritis and 2 cases of chronic pyelonephritis. Effective rate of cephradine to pyelonephritis was 70%. As a side effect with cephradine, gastrointestinal disturbance was noticed in 2 cases of chronic pyelonephritis. No change was recognized on general hematological findings, hepatic function nor renal function.

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A new antibiotic cephradine was studied on its antibacterial activity, absorption and excretion, level in organs, and clinical effect as well, and the following results were obtained.
1. Susceptibility of cephradine was distributed among 0.8-≥ 100 teg/m1 and 6.3-≥ 100 mg/ml respectively with Staphylococcus (45 strains), and E. coli (50 strains) and Kiebsiella pneumoniae (50 strains). A close correlation was observed between cephradine and cephalexin.
2. Peak af serum level was attained 1 hour after 500 mg or 1, 000 mg were administered orally at fasting in healthy adults, and the mean values were 4.94 μg/ml And 15.23 μg/ml respectively, exhibiting a clear dose response. Half life of the drug was 1.8 hours with two doses. Peak of serum level was attained 2 hours after 500 mg were administered orally 30 minutes after meal, value being lower than that at fasting.
Cephradine was administered orally at fasting at a dose of 500 mg in 3 patients of chronic renal insufficiency, and peak of serum level was attained 1 hour after the administration, value being 17.7 μg/ml. Half life of the drug was 18.1 hours.
Cephradine was administered orally at a dose of 500mg at fasting in healthy adults, and urinary recovery of the drug was about 70% within 6 hours.
3. Cephradine was administered orally once at a dose of 50 mg, 100 mg and 200 mg in rats to measure the drug concentrations in various organs. The values were overwhelming high in kidney and liver, and yet no clear dose response was noticed in two organs, and the concentraion ratio of oragns to serum tended to stop an increase.
4. Cephradine was applied clinically in 1 case of acute tonsillitis, 5 cases of acute bronchitis, 3 cases of acute cystitis, and 1 case of acute cholecystitis, totalling thus 10 cases, and the results obtained were excellent or good in all the cases treated. As a side effect of the drug, gastrointestinal disorders as anorexia and nausea were observed in 2 cases.

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1. Cephradine, a new cehpalosporin derivative, was administered orally in mice to determine serum and organ levels of the drug. The levels at one hour after dosing ranked in order of kidneys, liver, serum and lungs.
2. Cephradine was administered clinically to four patients. Good clinical effect was obtained in each one case of respiratory infection and urinary tract infection, while no good response was shown in two casesof cholecystitis.

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Susceptibility to cephradine was measured on 50 strains of Staphylococcus aureus isolated clinically. The values obtained were as high as those to cephalexin, minimum inhibitory concentration of both drugs ranging mostly between 1. 6 to 3.2μg/ml. On the other hand, susceptibility to cephradine was determined on 50 strains of E. coli isolated clinically, and the values obtained were rather lower than those to cephalexin. Cephradine was administered orally in 5 healthy volunteers at a dose of 500 mg, and both blood level and urinary excretion rate were high and reached almost the same levels as with cephalexin. Blood levels of cephradine were higher after the administration at fasting than after that with meal, absorption being higher and more rapid in the former than in the latter.
Cephradine was applied clinically at a daily dose of 1-2 g for 3-29 days in 13 cases of respiratory tract infection and 3 cases of urinary tract infection. The results obtained were satisfactory ; good in 12 cases and failed in 3 cases. No side effects were seen with cephradine, except mild eruption in 1 case and gastrointestinal disturbance in 2 cases.

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Cephradine was administered orally at a dose of 2 g for 14 days as a rule to 12 cases of bacterial pneumonia, and the effects of the drug were investigated centering around subjective symptom, leucocyte count, sedimentation rate and chest X-ray finding.
As a result, 1 case wes excellent which showed a clear improvement of various symptoms and test findings, 9 cases were good which presented a clear improvement within 7 days, and 2 cases were fair which demon-strated a clear improvement finally after 14 days.
No side effect was observed with the drug throughout all 12 cases.

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Antibacterial activity of cephradine was measured on the bacteria freshly isolated from patients, and then cephradine was applied clinically.
As for the antibacterial activity of cephradine, MIC was determined by standard method of the Japan Society. of Chemotherapy on E. coli 28 strains, Staphylococcus 18 strains, Klebsiella, Pseudomonas aeruginosa and others, totalling 83 strains. E. coli exhibited 6.25μg/ml in 23 strains out of 28 strains, without resistant strain, and yet mostly 1 to 2 grades higher than the values of cephalexin and cephaloridine of which the measurement was made simultaneously. Klebsiella presented 6, 25μg/ml, while Pseudononas aeruginosa was resistant in all 11 strains. Staphylococcus showed 1. 56μg/ml in 11 out of 18 strains, besides resistance of more than 50 μg/ml in 2 strains. In comparison with the values of cephalexin and cephaloridine, they were the same as in the case of E. coli.
As to the clinical trial with cephradine, the patients totalled 20 cases, including 4 cases of pyelonephritis, 15 cases of bronchitis and. 1 case of other. Among 4 cases of pyelonephritis, cephradine was effective in 3 cases and_ ineffective in 1 case. Among 15 cases of bronchitis, 13 cases were effective and 2 cases were ineffective.
As a side effect with cephradine, eruption was noticed in 1 case after an administration. No abnormality Was demonstrated in blood cell counts, liver function test nor renal function test.

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Laboratory and clinical studies have been carried out on a new antibiotic cephradine, and the following results were obtained.
1. No large difference was noticed between antibacterial activity of cephradine and that of cephalexin against both standard strain of Staphylococcus and isolated strain from lesion.
2. Cephradine was administered orally in rats to determine levels in blood and various organs. The level of cephradine was higher than that of cephalexin, especially remarkably in portal vein. Lung level of cephradine was, however, lower than that of cphalexin.
3. Bile level and excretion amount of cephradine in perfusing isolated liver of rat, were distinctly higher than those of cephalexin. The results were compared with other cephalosporin antibiotics, and yet cephradine showed to be superior similarly to cefazolin.
4. Cephradine was administered clinically in 12 cases of internal infections under middle grade mainly of respiratory tract infection, and the results obtained were remarkably effective in 2 cases, effective in 6 cases, ineffective in 2 cases and unknown in 2 cases.
No noteworthy side effect was, observed with cephradine, except serum transaminase activity rose slightly in a case.

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Cephradine was applied in 1 case of lobar pneumonia, 3 cases of acute pneumonia, 3 cases of acute bronchitis, and 5 cases of acute tonsitlitis, totalling 12 cases, and the clinical effects were investigated.As a result, there were obtained remarkably effective in 2 cases and effective in 2 cases for pueumonia, remarkably effective in 1 case and slightly effective in 2 cases for acute bronchitis, and remarkably effective in 3 cases and effective in 2 cases for acute tonsillitis. The drug was administered at a daily dose of 1.5-2g for 4-27 days, mostly for around 10 days. The effectiveness of cephradine may be awaited for pneumonia too. No noteworthy side effect was encountered with cephradine.

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Studies were made on cephradine, a new semi-synthetic cephalosporin antibiotic developed by Squibb Laboratories in U. S. A. The results obtained were as follows.
1) The MIC of cephradine was 6. 2-25pg/ml against 27 strains of Staphylococcus aureus isolated from human infections foci, and 12. 5-25g/ml against E. coli or Klebsiella. The antibacterial pattern of cephradine resembled to that of cephalexin.
2) Twenty-one clinical cases, consisting of 13 cases of respiratory infections and 8 cases of urinary tract infection, were treated with oral administration of cephradine at a daily dose of 1-1.5g. As a result, effectiveness was found in 15 cases of them. No marked side effects were observed with the antibiotic.

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By comparing the in vitro antibacterial activity of cephradine with that of cephalexin, almost the same degree was noticed between both.
No wide difference was observed between the blood concentrations after oral administration of cephradine and those after oral administration of cephalexin.
From the above results, the cliniacl effect of cephradine was expected to be almost the same as that of cephalexin.
The experience was described on 2 cases of respiratory infections treated by cephradine.

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Laboratory and clinical studies have been performed on a new antibiotic of cephalosporin family, cephradine, and the following results were obtained.
1. Antibacterial activity of cephradine was compared with that of cephalexin on 60 strains, in total, consisting of bacteria isolated from various clinical materials (Gram-positive bacteria 195 strains and Gram-negative bacilli 481 strains) and standard strains preserved in our Department 21 strains. As a result, antibacterial activity of cephradine was almost the same as that of cephalexin against all species, while 1 grade inferior against Klebsiella.
2. Cephradine was administered orally 1 hour after meal in healthy adults to compare both blood concentration and urinary recovery with those of cephalexin by means of a cross over test. Peak of blood level was 8.6μg/ml on the 1st hour on an average, while 17.1μ/ml with cephalexin. Cephalexin seems to present rather higher concentration than cephradine, though a relation was not denied with diet. Cephradine was excreted at 86.9% on an average within 6 hours.
3. As for the organ levels in rat, they were the highest in kidney, followed by liver, serum and lung in order.
4. Cephradine was applied clinically in 5 cases of respiratory infections, and the results obtained were remarkably effective in 1 case, effective in 2 cases, and slightly effective in 2 cases. As a side effect with cephradine, SGOT and SGPT values rose slightly in 1 case, and they were normalized following the drug interruption.

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Structural formula is similar each other between cephradine and cephalexin as well as action mechanism. The present authors have examined the in vitro antibacterial activity against various bacteria, and the antibacterial activity was almost the same between two drugs, similarly to the results reported by UEDA, OHSUKI and others. The measurement of the concentrations in serum and sputum resulted in the similarity between two antibiotics, and yet rather higher values were obtained with cephalexin than with cephradine in regard to the blood concentrations tested by cross over method. UEDA reported that the blood levels of cephradine were closely similar to those of cephalexin.
Cephradine was applied clinically in both acute and chronic respiratory infections, and the results obtained were effective in 9 cases out of 11 cases for the acute, while effective in 4 cases out of 8 cases for the chronic. Bacteria isolated from ineffective cases consisted of 2 cases of Pseudomonas aeruginosa and 2 cases of Grampositive bacillus.
BENJAMIN reported a high effective ratio as 95%-100% in upper and lower respiratory tract infections, all isolates being sensitive to cephradine.
In contrast to this, KLASTERSKY reported a high ineffective ratio of 42%, that is, 9 cases out of 21 cases of respiratory infections.
From the above results, cephradine may be expected to demonstrate an almost the same effect as cephalexin, both in vitro results and clinical ones.

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Oral cephradine, a new cephalosporin antibiotic, has a similar structure to that of cephalexin. The present authors have used this antibiotic clinically in 22 cases of lower respiratory infection and other various infections at a daily oral dose of 20-50 mg per kg for 2-14 days.
The rate of effectiveness amounted to 91% in all the cases treated. No clinical side effects nor remarkable change in blood findings and hepato-renal functions were encountered which may be ascribed to the medication of cephradine.

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Laboratory and clinical investigations were performed on cephradine in the field of pediatrics.
The in vitro antibacterial activity of cephradine is almost the same as that of cephalexin against Staph. aureus, while that of cephradine is rather inferior to that of cephalexin against enteric Gram-negative bacillus. The formation of filament and spheroplast was compared between both drugs using E. coil NIHJ, andthe result was nearly the same between both, while the bactericidal action of cephradine is far weakerthan that of cephalexin. No special finding was observed on the absorption and excretion of cephradine. The clinical course was described on 11 cases. As a side-effect with cephradine, urticarial eruption was noticed in 2 cases.
Although a slight difference is recognized between the antibacterial activity of cephradine and that of cephalexin (with almost the same chemical structure), it affects scarcely the clinical result. Cephradine maybe useful similarly to cephalexin for the adequate infections of children.
A slight difference was observed between the chemical structure of cephradine and that of cephalexin with almost the same structure, and yet an influence was scarcely noticed on the clinical results with the former antibiotic. It may be concluded that cephradine is useful nearly similarly to cephalexin in the adaptable infantile infections.

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Clinical studies were conducted on cephradine granule in the field of pediatrics, and the following results were obtained.
1) The changes of bacterial flora of feces were studied after the administration of cephradine on 3 infants of diarrhea. E. coli decreased mederately during the treatment, while other bacterial flora were not changed.
2) The skin tests of this drug were performed similarly on penicillin, anpicillin, chloramphenicol and cephalexin on 19 allergic children. Three of them showed positive skin test to cephradine without correlating to penicillin, which may suggest that an attention should be paid in using this drug in the allergic patients.
3) The clinical effects of cephradine were sufficient in 23 cases of infectious diseases. The prompt improvement of clinical signs was obtained in 18 out of 23 cases without side effects, whereas a vomiting occurred in 1 patient of 3 years girl soon after the administration and the use of cephradine was obliged to be interrupted.

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The dry syrup and capsule of cephradine, cephalosporin derivative for oral use, were administered in the field of pediatrics, and the following results were obtained.
1) The peak of blood level attained highly as 9. 5μg/ml on an average after the oral administration of 0. 25 g, but the concentration lowered remarkably after 5 hours. The urinary recovery ratios were distributed between 54. 7-99% of the dose within 5 hours. These results resembled to those of cephalexin.
2) The MIC against A group hemolytic Streptococcus was distributed between 0. 0.25-0. 1μg/ml, without resistant strain. The sensitivity of cephradine was similar to that of cephalexin.
3) The syrup and capsule of cephradine were administered clinically to the patients of scarlet fever at a daily dose of 30-40mg/kg for 7 days, and the results obtained were remarkably effective both bacteriologically and clinically.
4) The local or general (Kitter type) Staphylococcal exanthema due to Staphylococci low sensitive or nonsensitive to usual antibiotics, exhibited mostly a clinical effect by the administration of 40-80 mg/kg/day of cephradine.
5) The infections of upper respiratory tract or lower respiratory tract (bronchitis and bronchopneumonia) showed mostly effective or remarkably effective result by the administration of 40-80 mg/kg/day of cephradine, and the treatment was continued for 9-12 days in only bronchopneumonia.
6) The clinical results of cephradine were considered generally to be rather superior to those of pivampicillin, a new broad spectrum synthetic penicillin.
7) No digestive disorders were observed throughout cephradine dry syrup administration (37 case in total) and cephradine capsule administration (22 cases), totalling thus 59 cases.
8) No abnormal findings were encountered in S-GOT, S-GPT, BUN and blood during cephradine administration for 7-12 days at a dose of 40-80 mg/kg/day.
9) From the above treatment results, a general dosage of cephradine was considered to be 30-80 mg/kg /day in the pediatric infections due to cephradine sensitive bacteria.

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Cephradine was administered to the children of infectious diseases, including 4 cases of pneumonia, 3 cases of acute bronchitis, 3 cases of angina lacunalis, 6 cases of acute pyelocystitis and 4 cases of purulent lymphadenitis, totaling 40 cases.
Clinical effectiveness was obtained in 16 out of 20 cases, and bacteriological effectiveness in 12 out of 17 cases excluding 3 cases with unknown bacteria.
Hematological, renal and hepatic function tests were performed in all the cases treated beforeand on the completion of cephradine therapy, and no untoward laboratory findings were noticed. No side reactions were encountered neither throughout the clinical course of cephradine treatment.

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The present authors have carried out the laboratory and clinical studies of cephradine, and the results were obtained as follows :
The drug sensitivity was measured by a plate dilution method on 31 strains of Staph. aureus and 22, strains of E. coli both isolated from patients.
The growth of Staph. aureus was inhibited in 87. 0% at a concentration of less than 6. 25 μg/ml of the drug, while that of E, coli was in 71. 0% at a concentration of less than 25. 0 pg/ml of the drug.
Cephradine dry syrup was given orally once at a dose of 25. 0 mg per kg of body weight to 2 children. The blood level of the drug reached the maximum of 18. 5 μg/ml 1 hour after the administration, whereas it was not determined 4 hours after the administration.
Cephradine dry syrup was effective clinically in 7 out of 9 cases of pediatric infections.
As a side effect with the drug, eosinophilia occurred in 2 patients and diarrhoea in 1 respectively.

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Absorption and excretion of cephradine dry syrup, a new derivative of cephalosporin C antibiotics, was studied, and its clinical effects were evaluated in the treatment of 69 patients with acute bacterial infections in children.
1) Blood concentration of this antibiotic was measured in 5 children after a single oral administration of 12. 5 mg/kg. Its concentration was maximum (8. 6 μg/ml) at 1 hour, 4. 9 pg/ml at 2 hours, and too low to be determined at 4 and 6 hours, respectively. An average urinary recovery rate was 82. 4% in 6 hours. A cross over test was performed in 3 out of these 5 children using 12. 5 mg/kg and 25. 0 mg/kg, and showed a definite dose response. Food ingestion appeared to exert little influence on absorption of this antibiotic.
2) Approximately 50 mg/kg of this antibiotic was given daily to 30 patients with urinary tractinfection. Its efficacy rate was 60. 0% in the cases with obstructive uropathy and 95. 0% without it, averaging 83. 3% throught all cases. The average day of disappearance of the cardinal signs and symptoms was estimated in the cases with excellent and good results : (The day of start of treatment was calculated as day 1) causative organism 3. 0 day, fever 2. 2 day, pollakisuria 3. 3 day, miction pain 2. 2 day, urinary protein 3. 5 day, and urinary white blood cells 3. 9 day.
3) An efficacy rate was 94. 1% in 34 cases of tonsillitis when the same dose of this antibiotic was given. The average day of disappearance of the cardinal signs and symptoms was as follows in the cases with excellent and good results : causative organism 3. 3 day, fever 2. 6 day, tonsillar injection 4. 2 day and white coat 4. 1 day.
4) It was also given in 2 cases of suppurative lymphadenitis and in each 1 case of pneumonia, purulent omphalitis and salmonella enteritis. The results were either excellent or good except for in salmonella enteritis in which this antibiotic was ineffective.
The overall efficacy rate in 69 cases was 88. 4% : excellent in 33 cases, good in 28 cases, and failure in 8 cases.
5) Among 69 cases, diarrhea was observed in 3 cases and skin rash in 2. They were all temporary and were not severe enough to withdraw the medication. The clinical study of this antibiotic was conducted for a period of about 8 months, but the above symptoms were all observed only during a short period of time. It was therefore doubtful whether they represented adverse reactions of this antibiotic.
6) Laboratory examinations were performed in all patients. Urinalysis was negative in all. Peripheral eosinophilia was observed in 2 cases without accompanied by allergic symptoms. An elevation of GOT was noted in 6 cases, in 2 of whom GPT was also elevated, and BUN was found to be increased in 6 cases with a concomitant increase of NPN except for in 1 case. The elevations of these chemical parameters were all temporary. Frequency of such abnormalities in laboratory examination is roughly equal to that observed in clinical trials of other antibiotics and can not solely be ascribed to this antibiotic. Consequently it was considered that the adverse reactions of this antibiotic do not outnumber those of other antibiotics.
7) Taste and flavor of this antibiotic was accepted to children.
8) The above results with cephradine dry syrup are comparable to those obtained with cephalexin. Slightly faster absorption and excretion of cephradine compared with those of cephalexin may be either advantageous or disadvantagenous. Based on the above results, it was concluded that cephradine dry syrup is a potent new antibiotic in pediatric infections.

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Cephradine is a new cephalosporin antibiotic with the structure similar to that of cephalexin. Thirty-nine children were treated orally with cephradine dry syrup.
Twelve of 16 patients with respiratory infections (Klebs. 4, Staph. aureus 3, Strept. 3, E. coli 3, GPC 1, GPB 1 patient) obtained a successful result, while 4 failed.
Sixteen of 19 patients with skin and soft-tissue infections (Staph. aureus 16, Prof. mirabilis 1 patient) had a satisfactory result in each instance, while 3 patients were judged to present an indeterminate result.
One of 3 patients with urinary-tract infections had a success, another one failed, and the remaining patient was difficult to be evaluated.
One patient with enteritis responded satisfactorily.
As a result of the treatment, excellent was obtained in 12 patients, good_ in 18, failure in 5, and remaining 4 were judged to have an indeterminate result, clinical cure rate being thus 85. 7%.
One patient experienced a transient skin eruption and another patient a mild diarrhea. No serious toxicity occurred, however, in this group of patients treated with cephradine dry syrup.
From the results obtained in this study, cephradine dry syrup seems to be useful in the treatment of infectious diseases of children caused by gram-positive and gram-negative microorganisms.

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Cephradine dry syrup was administered in 80 cases of urinary tract infection of children, and its clinical and biological effects were investigated.
A daily dose of 30-50 mg/kg divided in 4 was administered for 20 days on an average, and the effective ratio obtained was 90% from overall judgement and 73% from bacteria count. Being classified by causative bacteria, the effective ratio was 89% from overall judgement and 74% from bacteria count with E. coli, and though cases are few with other bacteria, the results were excellent in 9 cases out of 11 cases, and poor in 2 cases with Proteus, poor in 1 case of Citrobacter, excellent and good respectively in 1 case with Klehsiella, excellent in 6 cases and poor in 3 cases with Enterococcus, and excellent with Staph. aureus.
Antibacterial activity of cephradine was similar to that of cephalexin against E. coli, Proteus. Cit robacter, Klehsiella, Enterococcus and Staph. aureus.
As a side effect with cephradine, no complaint was noticed as gastrointestinal symptom, eruption or eosinophile. GOT, GPT, ALP and BUN were tested to examine hepatic and renal functions, and the variation of values obtained were all in a range of normal values, taking into consideration underlying disease, complication and effect of hemolysis on test.
From the above results, it may be concluded that cephradine is an effective drug for urinary tract infection of children.

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Cephradine dry syrup was administered to the patients of bacterial infetions of children, and the clinicaland bacteriological investigations were performed.
A daily dose of 27-100mg/kg of the drug divided into 4 was administered for 17 days on an average, andthe synthetic effect obtained was 88%, while the bacteriological one remained at 60%.
Antibacterial activity of the drug was closely similar to that of cephalexin against 3 species ; β-hemolyticStreptococci, Staph. aureus and E. coll.
As a side effect of the drug, no case, was encountered which showed gastric symptoms nor eruption. Todetermine the effect of the drug on liver and kidney, GOT, GPT, ALP and BUN were examined, and no case was observed which exhibited an abnormal value after the administration, except an eosinophile was noticed in 2 cases, of which the effect may be attributed both to underlying disease or complication.

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Laboratory and clinical investigations were performed with cephradine, and the following conclusions were obtained.
1) Antibacterial spectrum : Cephradine demonstrated an almost the same antibacterial activity as that of cephalexin both with Gram-positive cocci and Gram-negative bacilli.
2) Sensitivity distribution of bacteria isolated from surgical fields : Cephradine exhibited an antibacterial activity against Staph. aureus, E. coli, Klebsiella pneumoniae and Proteus vulgaris. In comparison with the results of cephalexin, cephradine presented an almost the same cephalexin against Staph. aureus and Proteus vulgaris, inferior to cephalexin against E. coli, while superior to cephalexin against Klebsiella pneumoniae.
3) Serum level and urinary excretion : By means of cup method using Moni-trol as standard, serum level was measured after 500 mg of cephradine were administered orally at fasting, and a peak of 12.2μg/ml was attained 1 hour after the administration, and a value of 0.8μg/ml remained even after 6 hours. As to the urinary excretion, the highest value was obtained 1-2 hours after the administration indicating 3, 390-4, 133 pg/ml on an average, and the urinary recovery rate was 90.2% within 6 hours.
4) Level in organs : Cephradine was administered orally at a dose of 20 mg/kg to 1 group of 3 SD rats, and the level was high in kidney and liver, followed by serum, spleen, lung and heart in order. Values of liver and kidney were especially always higher than serum level. Level in urine showed a peak of 2, 000μg/m1 2 hours after the administration. Level in bile attained a peak of 176.5 pg/ml 4 hours after the administration.
5) Metabolism in vivo : Metabolism in vivo was investigated using human urine. Bioautogram was prepared by thin layer chromatography of diluted urine, and it was proved that cephradine is not metabolized in vivo.
6) Separation and quantitative analysis of cephradine and cephalexin in urine : Separation and quantitative analysis of cephradine and cephalexin in urine were measured by means of high pressure liquid chromatography. As a result, it was proved that cephradine is excreted without being metabolized in vivo.
7) Results of clinical application : Cephradine was applied to 9 cases of surgical infections. Results obtainedwere effective in 7 cases, and ineffective in 2 cases. No noteworthy side effect was encountered with cephradine.

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The present paper deals with the MIC, concentration in tissues and clinical effect on cephradine (abbr. CED).
The MICs of cephradine against Staph. aureus and E. coli are all 1 dilution grade lower than those of cephalexin, values being distributed between 6. 25-0. 39 pg/ml and 2. 5, ..., 6. 25 itg/ml respectively. Asto the concentrations of cephradine in tissues, transfer in kidney is quite excellent, values at 30 minutes exhibiting about 10 times in serum and about 2 times in liver.
As for the clinical effects of cephraine, the effectiveness was obtained in 17 cases out of 23 cases of superficial soft tissue infections, effective ratio being 74%.
Cephradine may be thus used satisfactorily for the infections of middle grade centering around urinary tract infection, similarly to cephalexin which is widely employed as an oral cephalosporin antibiotic.

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Some laboratory experiments have been made on a new antibiotic cephradine, and this drug has been applied clinically in an oral preparation in the surgical infections. The following conclusions were reached.
(1) Antibacterial activity
Antibacterial activity of cephradine and cephalexin against Staphylococcus aurens and Escherichia coli isolated from surgical lesions, demonstrated almost the same sensitivity with two drugs.
(2) Absorption and excretion
Cephradine (500 mg) and cephalexin (500 mg) were administered once at fasting in 3 healthy adults, and blood level and urinary excretion were examined by cross over test. Both blood level and urinary excretion showed almost the same pattern with two drugs.
Biliary excretion was measured in 5 clinical cases. Both cephradine and cephalexin were excreted well in bile, and the biliary excretion was obstructed by the presence of abnormality in hepatic function with both drugs.
(3) Result of clinical application
Cephradine was applied mainly in acute suppurative infections of soft tissues in the field of surgery. Out of 26 cases treated, the results obtained were excellent in 5 cases, good in 12 cases, fair in 7 cases and poor in 2 cases, effective ratio being 92. 3% including fair cases. As a side effect with cephradine, one patient complained of a pain in epigastric region, and yet the drug interruption was not necessary. In other cases, no abnormality was observed in hepatic and renal functions so far as the tests were performed.

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Effectiveness of cephradine, a new semisynthetic cephalosporin, was studied in 28 patients with acute infections of soft tissue in surgical field.
Cephradine was administered orally at a daily dose of 1, 000, 1, 500 and 2, 000 mg for 4-21 days.
The overall effective rate was 90. 0% excluding 2 undecided cases.
Satisfactory results were obtained in patients infected by Staphylococcuus aureus. The failure was noticed, however, in 2 patients of postoperative perineal fistula infected by Escherichia coli and of leg ulcer infected by Pseudomonas aeruginosa.
As a side effect, 1 case complained of pyrosis.

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A new antibiotic cephradine has an excellent antibacterial activity against Staph. aureus, and may be effective against E. coil and Kiel. pneumoniae among Gram negative bacilli. The antibacterial activity of cephradine is similar to that of cephalexin. In the investigation on its absorption and excretion, a high blood concentration is obtained as 10 μg/ml 1 hour after an oral administration of 500 mg, and an excretion in urine is excellent as well. Cephradine is expected thus to be very useful with a little side effect as an oral drug for the infe-ctions in surgical field. The bile concentration of the drug varies fairly by case. Cephradine may be expected to be effective considerably if the drug is administered at an adequate dose.

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Cephradine was applied clinically in 20 ceses of bone and joint infections, and the results obtained were remarkably effective in 7 cases, effective in 5 cases, slightly effective in 5 and not effective in 3 cases.
These treament results were investigated in view of detected bacteria and lesional conditions.

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Double blind test has been performed on cephradine, a new cephalosporin antibiotic for oral use employing as an active placebo cephalexin, an antibiotic already fully studied and widely applied among the family, to evaluate cephradine as impartially as possible.
As an objective disease, acute suppurative infection of soft tissue was chosen in surgical field, excluding the patients with obscure onset and course of the disease. Those with severe underlying disease and complication were excluded too, age being limited to above 16 years. Both drugs were administered orally 3 times daily at a dose of 500 mg for 7 days as a rule.
As a result, no significant difference was observed between two drugs under the same conditions both in clinical and bacteriological views. As a side effect with the drug, no difference was noticed, without encountering any trouble disturbance.

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Cephradine, a new oral autibiotic of the cephalosporin C, was evaluated through laboratory and investigations. The results were as follows.
1) In measurement of MIC by agar plate dilution method, spot inoculum method was proved reliable as well as the standard streak method.
2) The MIC of cephradine against E. coli, determined by the spot inoculum method, showed slightly lower than the other derivatives of cephalosporin C.
3) Our clinical experience confirmed, however, a good efficacy with cephradine in female patients of uncomplicated acute cystitis.
4) No side effect was observed.

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A new semisynthetic cephalosporin antibiotic, cephradine was used for 60 patients with acute cystitis.
Cephradine was administered orally for 3 days at a daily dose of 1.0 g.
The therapeutic results were as follows, 54 cases were excellent, 4 cases good and 1 case poor.
No side effect was noticed. Most strains of E. coli ware inhibited at cephradine concentration of 6.25μg/ml or less.

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Cephradine was applied in the infections of urinary tract, and an excellent effect was obtained especially for acute simple cystitis.
No proportional relationship was noticed between dosage and effect in view of the treatment effects classified by disease and bacteria, and yet a satisfactory effect was obtained with a dosage of 1, 000 mg.
As for the side-effect, no severe crisis occurred, and the safety was confirmed with the drug. Blood was taken before and after drug administration from some of the patients to examine the blood, hepatic and renal disorders, and there proved no influence which may be due to the drug.
The MIC was measured on cephradine and cephalexin, and a difference was scarcely noticed between both.

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The investigation has been made on the antibacterial activity of cephradine and its therapeutic evaluation in urinary tract infections, and the following results were obtained.
1. The antibacterial activity of cephradine was measured on each 50 strains of E. coli and Staph. aureus recently isolated from lesions to compare with that of cephalexin. The frequency of resistant bacteria was similar between Gram-positive and-negative bacilli, and yet the MIC of cephradine showed frequently to.be lower sensitive than that of cephalexin in E. coli.
2. Twenty-one cases of acute urinary tract infections, 10 cases of chronic urinary tract infections and 3 cases of prostatitis were treated with 1, 000-2, 000 mg of cephradine divided into 3-4 times daily for 3-14 days. Among the 34 cases, excellent effect was found in 16 cases and good effect in 9 cases, positive rate being 73.5%.
3. No side effects were observed with cephradine throughout all the patients treated.

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Cephradine was administered clinically at a daily dose of 2 g for 3-7 days for acute urinary tract infection, and the effective ratio obtained was 71%. As a side effect with the drug, gastric malaise was observed only in 1 case. Cephradine was administered without anxiety.

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Cephradine is a new antibiotic closely similar to cephalexin. The present author has performed previously the clinical treatment of gonorrhea with cephalexin, and the curative ratio obtained was 75% in the group administered 1 g, and 100% in the group administered more than 2 g. Taking a view of gonococcus of which antibiotic resistance has become stronger, cephradine may be a satisfactory antibiotic to treat gonorrhea, as the curative ratio of 80% was obtained with 2 g of the drug. Cephradine will be a necessary antibiotic for the treatment or gonorrhea, as it exhibited especially a remarkable effect in the cases due to CP resistant gonococcus or those due to penicillin resistant one (Case 7, 4 and 15).
It is noteworthy that a case due to TC resistant gonococcus was encountered among the meffective cases, and the investigation should be pursued on the relation between TC and cephradine.

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Cephradine (CED) was applied clinically in 20 cases of tract infection, and the results were obtained as follows.
1) Among 14-ases of acute urinary tract infection, the results obtained were excellent in 13 cases and fair in 1 case, effective ratio being 92.8%.
Among 6 cases of chronic urinary tract infection, the results were excellent : in 3 cases and poor in 3 cases, effective ratio being 50%.
On the whole, 20 cases resulted in excellent in 16 cases, fair in 1 case and poor in 3 cases, showing 80% as effective ratio.
2) MIC of cephradine and cephalexin was measured against various bacteria, and the antibacterial.activity of cephalexin was 1-2 grades stronger than that of cephradine against. E. coli and Klebsiella.
This was noticed similarly against Staphylococcus, Pseudomonas and Gram-positive diplococcus.
3) As a side effect with the drug, GOT and GPT values rose in one case.

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Basic and clinical studies were carried out on cephradine, a new semisynthetic cephalosporin.
1) Susceptibilities to cephradine and cephalexin were tested on 146 strains newly isolated from genitourinary tract infections. The results indicated that antibacterial activities and sensitivity distributions to cephradine were almost the same as those to cephalexin.
2) Bacterial growth rate in a medium containing cephradine or cephalexin was observed by means of a biophotometer (BIO-LOG 11). The influences were investigated about the antibiotic concentration, inoculum size of organism (E. coli NIHT JC-2), morphological change, and MIC after the experiments.
The growth rates in the presence of cephradine were almost the same to those in the presence of cephalexin in various experiments. The MIC's after experiments were not greatly changed from that of before those cultures.
Both antibiotics gave similar results each other in the biophotometric studies, except that cephradine seemed to have a tendency to promote filamentation than cephalexin.
3) Thirty-one patients with genitourinary infections were treated with cephradine at a daily dose of 1 g for 3 or 4 days, and the therapeutic results were evaluated both clinically and bacteriologically.
All the acute infections (16 cases) responded well to the drug, and good results were obtained in 11 out of 15 chronic cases (73%).
4) No side effect was observed throughout the course of the treatment of cephradine, except for nausea only in one case.

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1) Blood concentration
Cephradine was administered orally once at a dose of 500 mg in 2 healthy adults, and a peak of blood concentration was attained 1 hour later, value being 13.6 μg/ml on an average. The value of 0. 4 μg/ml was noticed even after 6 hours.
2) Urinary recovery ratio
Cephradine was administered orally at a dose of 500 mg in the same cases in which blood concentrations were measured, and urinary recovery ratio obtained within 6 hours was 84.5% on an average.
3) Result of clinical application
Cephradine was applied clinically in 55 cases of urinary tract infection, and the results obtained were excellent in 36 cases, good in 12 cases and poor in 7 cases, effective ratio being 87.3%.
4) Side effect
Side effect with cephradine was encountered in 6 cases out of 55 cases (10.9%), including gastrointestinal disorder in 3 cases, laryngeal pain in 1 case, exanthema in 1 case, and tinnitus and palpitation in 1 case. Administration of the drug was interrupted in 1 case of exanthema and 1 case of tinnitus and palpitation.

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