The direct effects of fosfomycin sodium (FOM-Na) upon GOT and GPT activities and upon intervention to the methods for determination of these enzymes, and the hepatotropic toxicity of FOM-Na have been investigated in the present study using various experimental animals.
(1) Upon incubation of 1ml each of sera of mice, rats, and dogs with 1.6, 5, and 10 mg of FOM-Na the GOT and GPT activities in these sera were determined with WROBLEWSKI-KARMENm ethod and REITMAN-FRANKEL method. The results revealed that FOM-Na had no interference on GOT and GPT activity measurement.
(2) After single intravenous injection of 500mg/kg of FOM-Na, blood samples were collected at intervals up to 3 hours after the administration and the GOT and GPT activities of these serum samples were determined with WROBLEWSKI-KARMEN method and REITMAN-FRANKEL method. The revealed no change in GOT or GPT values.
(3) After single administration of 500-1,000 mg/kg of FOM-Na and 0.5-1ml/kg of 10% olive oil suspension of carbon tetrachloride to rats or rabbits, activities of various enzymes in sera were determined at intervals and histology of liver was investigated. The results revealed that there was no enhanced hepatic toxicity of carbon tetrachloride by FOM-Na.
(4) The quantities of liquid from hepatic veins and activities of enzymes releasedinto theliquid through perfusion of extirpated liver of rats or rabbits with ROCK-RINGER'S solution containing 1 or 5mg/ml of FOM-Na were determined. The results revealed that there was no adverse effect of FOM-Na upon the quantity of the liquid from hepatic veins or release of enzymes.
(5) From the results of the above-mentioned experiments, it could be assessedthat FOM-Na does not intervene with the activities of GOT and GPT or with the method for determination of enzymes and that it has no hepatotropic toxicity.

View full abstract

Measurement of MICs of PC-904, CBPC and GM against 135 strains of Pseudomonas aeruginosa isolated from patients with urinary tract infections was performed.
Susceptibility to PC-904 of Pseudomonas aeruginosa was found to be 3-7 times more sensitive than that to CBPC and as same as that to GM with inoculum size of 108/ml and 106/ml.
Serum level of PC-904 reached a peak of 38.5μg/ml 15 minutes after 0.5g intravenous administration.
Urinary recovery rate until 6 hours after the administration was 12.5%.
Overall clinical efficacy of 6 cases of acute simple cystitis and 3 cases of chronic complicated cystitis was judged to be 83.3% and 33.3% respectively by a criterion proposed by the UTI Committee in Japan.

View full abstract

The biological assay method of sisomicin was examined, and then absorption, distribution, metabolism and excretion of sisomicin after a single parenteral administration of 10mg/kg to mice, rats and dogs, and the persistence in the kidney and binding to serum protein were compared with those of gentamicin.
Agar-well and, cup methods using. Bacillus Subtilis as the test organism and nutrient agar as the medium revealed higher sensitivity than paper-disc method and gave the suitable standard curves. Paper-disc method, however, seems to be applicable to the assay for the usual concentration of sisomicin in the body fluids after treatment. The standard curve of sisomicin was markedly influenced by pH of medium and diluent, the higher the pH of them and the larger of the inhibited zone size. Human plasma and Moni-trol I as the diluent of standard solution gave larger zone size than phosphate buffer solution at pH 8.0, but no difference between the two diluents of human plasma and Moni-trol I was observed.
Sisomicin was extremely well-absorbed from injected sites of all animals such as mice, rats and dogs. Plasma levels of sisomicin following subcutaneous and intramuscular injections into animals decreased rapidly and exponentially. The biological half-life times of plasma concentration curves of sisomicin had a tendency to become longer in bigger animal species as 19.4, 23.5 and 75.6 minutes for mice, rats and dogs, respectively. Sisomicin was rapidly distributed into various organs of mice and rats after subcutaneous and intramuscular iNections. The concentration in kidney was very high and persisted longer than in plasma and other tissues. The concentrations in lung, heart, spleen and testis, were lower than those of plasma and decreased rapidly. Especially, the concentrations in liver of both animals were the lowest among the all tissues tested.
Total excretion rates in urine during 48 hours after administration were 68.9%, 81.2% and 92.7% of dose in mice, rats and dogs, respectively, whereas the excretion in bile during 24 hours was about 0.1% of dose in rats. The large part of sisomicin parenterally administered in animals was recovered in urine within 6 hours. However, very small amount was consistently excreted in urine for the period of 24-48 hours after injection. No active metabolite was found in urine of rats and dogs treated with sisomicin by means of thin-layer chromatography and bioautography.
Persistence of sisomicin in the organs of rats and dogs for 14 weeks and 7 weeks, respectively, after a single intramuscular injection was investigated. The tissue concentration-time curve for the whole kidney of rats was divided in the two characteristics of half-life times which were 2.4 weeks during the first 6 weeks and 8.6 weeks between the sixth and fourteenth week after treatment. In dogs, the concentration of sisomicin, in renal cortex decreassed more rapid with a half-life time of 1, 4 weeks than those in rats. On the other hand, the concentration in renal medulla and urine was extremely lower than in renal cortex and only detected until the first to third week after injection.
By means of ultrafiltration method, only small amounts, about 10%, of bound sisomicin to human, dog and rat serum were observed, but the percentages of bound sisomicin were 22.4% and 26.6% in rabbit serum and in 4% solution of human serum albumin, respectively.
No significant difference was observed in the pharmacological results between sisomicin and gentamicin, except for the biological assay method of sisomicin.

View full abstract

CS-1170 is a new antibiotic, a derivative of cephamycin C. In vitro, 50 strains of E. coli and Klebsiella consisting of gentamicin-sensitive strains isolated from the blood and gentamicin-resistant strains isolated from the urine were inhibited at concentrations from 0.4 to 12.5 mcg/ml of CS-1170, whereas only 2 strain of Klebsiella isolated from the blood had MIC more than 50 mcg/ml of the antibiotic. Moreover, CS-1170 was significantly more effective than cefazolin and cephalothin against these strains. Ten strains of gentamicin-sensitive Serratia isolated from the blood and the 2 gentamicin-resistant strains were inhibited at concentrations from 3.2 to 50 mcg/ml of CS-1170 and only one strain was resistant to this agent. All tested Serratia were resistant to cefazolin and cephalothin. CS-1170 was not effective against Enterobacter.
Three cases of biliary tract infections consisting of 2 cases of cholelithiasis and a case of carcinoma of bile duct were treated with 4g/day dosage of CS-1170. The remarkable effects were obtained in the two cases with cholelithiasis, whereas a case with the carcinoma was treated not so effectively by administration of CS-1170.

View full abstract

The following results have been obtained in our trial of CS-1170, in 2g piggy bag, on the respiratory tract infections:
1) CS-1170 was found to be effective in all the cases treated, including 6 cases in which CS-1170 was used alone. The cases treated with CS-1170 included those cases in which no other antibiotics had been used, as well as 5 cases in which other penicillins and cephalosporins were found to be ineffective or not adequately effective. The results indicate the usefulness of CS-1170 in the treatment of the respiratory tract infections.
2) Slight elevation of GOT and GPT was observed in one case as the side effect of CS-1170. No abnormality was found in other laboratory tests. The incidence of side effects of CS-1170 is believed to be not higher than those of other cephalosporins.

View full abstract

1. Cefmetazole was administered to 10 patients; 5 acute cholecystitis, 4 acute peritonitis and 1 periproctitis.
2. Cefmetazole was given by drip infusion at a daily dose of 2-4g.
3. Clinical response was excellent in 3 patients, and good in other 7 patients.
4. No clinical adverse effect was recognized except the increase of GOT and GPT in 1 patient.

View full abstract

[in Japanese]

View full abstract

CS-1170 was used in gynecological cases of infection, and the following satisfactory results were obtained.
1. The drug was markedly effective in 3 of 12 cases, effective in 7, and ineffective in 2, being the efficacy rate 83.3%.
2. It was highly effective even in the cases in which cefazolin (CEZ) and sulbenicillin (SBPC) were ineffective.
3. The results of the bacteriological examinations turned to negative in 7 cases, but continued to be positive in 2, being the bacteriological efficacy rate 77.7%. It is noteworthy that E. coli completely disappeared by the administration of CS-1170 in 2 cases in which CEZ was ineffective.
4. No side effect attributable to CS-1170 administration was observed.

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

The clinical effects and side effects of administrating sodium cefapirin to the stomatic infective diseases were examined in twelve cases. The following are the main results:
(1) The clinical results of the treatment were noted effective in one case, effective in nine cases and slightly effective in two cases.
(2) The results of renal function tests were as follows:
After the administration, it was observed that the values of Ccr test decreased in two cases, the values of PSP test decreased in one case, but the BUN values remained within the normal range in all cases. However, in all cases, no significant deviations were observed in the values of each test measured before and after the test.
(3) The results of hepatic function tests were as follows. The values of GOT and GPT showed slight decrease in majority cases. However, the difference between pro and post values was within the normal range and no significant deviations were observed.
(4) No side effects including drug allergy were observed in every cases.

View full abstract

The clinical effects of apalcillin (APPC) treatment for 7 patients with bile duct infections were investigated and the following results were obtained.
1) Clinical effectiveness: Of 7 patients treated with APPC, the results were good in 5 cases, fair in 1 case and poor in 1 case.
2) Absorption and excretion of APPC: One g of APPC was administered with one shot intravenously to 4 patients of which 2 were malignant tumor cases and the remaining 2 non tumor cases. A peak of APPC level in serum and bile was 79 μg/ml and 140 μg/ml respectively in malignant tumor cases and 96 μg/ml and 180 μg/ml respectively in non tumor cases.
3) Side effects of APPC: No significant side effects were observed in 7 patients treated with APPC, except abnormal elevation of S-GOT and S-GPT levels occurred transiently in 2 of 7 cases.

View full abstract

[in Japanese]

View full abstract

The hemolytic plaque test and the delayed cutaneous hypersensitivity test were used to demonstrate the interaction of antithymocyte globulin (ATG) and immunopotentiating activity of schizophyllan (SPG) in humoral and cellular immunity.
Although the administration of ATG 24 hours before the injection of antigen greatly decreased the number of plaque-forming cells (PFC), the recovery of PFC was recognized to some extent with the administration of SPG. The moderate decrease of PFC was seen with the simultaneous administration of ATG and antigen. In this case, the recovery of PFC by the administration of SPG was remarkable, reaching the same degree as that of control. When ATG was administered 24 hours after the injection of antigen, almost no decrease of PFC could be observed. In this case, the number of PFC was greater than that of control and less than that of the group treated with SPG alone.
In the delayed cutaneous hypersensitivity test with picryl chloride, the increase of ear thickness in mice treated with ATG was lower than that of positive control. The decrease was recovered by the administration of SPG up to the same degree of control, but not up to the degree of the group treated with SPG alone

View full abstract

Chronic toxicity and its recovery of pepleomycin sulfhte was studied in both sexes of beagle dogs.
At dose levels of 0.3, 0.15 and 0.075mg/kg, pepleomycin was administered intramuscularly to dogs for 180 successive days.Twod ogs of the 0.15mg/kg dose group were used for recovery test for 35 days.
As generalfindings, the decrease of food intake, the loss of body weight, ulceration of foot pad, nail root necrosis and onychoptosis, ulcer of tongue and labia, and alopecia, dermatitis and necrosis at friction sites were observed more severely in the 0.3mg/kg dose group of both sexes, especially in male, than those in bleomycin were.
In the dose groups of 0.15 and 0.075mg/kg, their findings were observed as slightly as those in bleomycin were.
The death occurred in the 0.3mg/kg dose group of both sexes.
The lesions of liver and kidney were recognized in the 0.3mg/kg dose group of both sexes, severely in male, on histopathological findings.
Additionally severe fibrosis of lung was observed in one of the 0.3mg/kg dose group of female.
In general chronic toxicity of pepleomycin was revealed more severely in the 0.3mg/kg dose group than that of bleomycin was, but in the dose groups of 0.15 and 0.075mg/kg difference between their toxicities was not significant.
In addition, chronic toxicity of pepleomycin in dogs showed more severely in male and its recovery was hardly recognized during its period.
The maximum safety dose in this studies was estimated to be between 0.075 and 0.15mg/kg in dogs.

View full abstract

[in Japanese]

View full abstract

NK 631, a new derivative of bleomycin, was clinically used in 14 cases of malignant tumors of skin.
The results obtained were remarkably effective in 7 cases, effective in 3 cases, slightly effective in 2 cases and ineffective in 2 cases. The effective ratio was 71%, when calculated regarding slightly effective as ineffective.
Compared with bleomycin, we were impressed that the side effects observed with NK 631 were similar to those with bleomycin, but the influences for lung were smaller and slighter than the latter.

View full abstract

[in Japanese]

View full abstract