[Pharmacokinetic studies of micronomicin using a continuous intravenous infusion method].

The basic pharmacokinetics of micronomicin (MCR) were studied in 4 healthy adult volunteers. MCR 60 and 120 mg were intravenously administered in 30 and 60 minutes at constant rates by means of continuous infusion apparatus. The same dosages were also tested by intramuscular route. The concentrations of MCR in serum and urine were determined by HPLC and analyzed following the two-compartment open model after intravenous treatment and following the one-compartment open model after intramuscular treatment. When MCR was given by intramuscular route, the mean serum concentration of 4 subjects reached a peak of 3.98 micrograms/ml at 30 minutes after a dose of 60 mg and 6.7 micrograms/ml at 30 minutes after that of 120 mg. The peak concentration was achieved at the end of intravenous infusion and was dose-related, since it was 6.1 and 10.5 micrograms/ml after a 30-minute infusion of 60 and 120 mg, respectively, and 4.85 and 9.43 micrograms/ml after a 60-minute infusion of 60 and 120 mg, respectively. At 8 hours, concentrations dropped to less than 0.1 microgram/ml and to 0.2 microgram/ml or less after 60 and 120 mg, respectively, regardless of the route and rate of administration. The mean urinary recovery up to 8 hours ranged 84 to 92% of the dose. There were no appreciable differences in pharmacokinetic parameters among 4 modes of intravenous infusion, with a T1/2(beta) of 1.43 approximately 2.02 hours. In the case of intramuscular treatment, parameters analyzed following the one-compartment open model were on similar levels to corresponding values found after intravenous treatment and the T1/2 was 1.39 hours after 60 mg and 1.43 hours after 120 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

[Absorption and excretion in constant infusion of cephaloridine (author's transl)].

Using 6 healthy adult male volunteers, who were divided in halves, the serum and urinary levels of cephaloridine were determined during and after 2-hour constant drip infusion of 2 g cephaloridine dissolved in 500 ml physiological saline solution (= Group I) and 1-hour constant drip infusion of 1.5 g solution (= Group II); besides, pharmacokinetic analysis was made for one-compartment and two-compartment models. On the basis of the values of serum levels obtained from this trial, pharmacokinetic parameters were calculated and simulation curves of serum levels for various doses (0.5 approximately 2 g) and duration (1 approximately 4 hours) of cephaloridine drip infusion were drawn.

[Pharmacokinetic studies of tobramycin using the continuous intravenous infusion method (author's transl)].

Tobramycin (TOB) was administered to 4 healthy adult volunteers (mean body weight 63.5 kg, surface area 1.71 m2) as one time 90 mg dose by intramuscular injection or by intravenous infusion (30 or 60 minutes) in a crossover study. Serum and urinary concentrations were assayed by bioassay and radioimmunoassay (RIA). Pharmacokinetic analysis was done with a one-compartment open model in the case of intramuscular injection and a two-compartment open model in the case of intravenous infusion. The correlation constant was 0.92, and the relation formula was y = 0.81x+0.13 between bioassay and RIA. In the case of intramuscular injection, the peak serum concentration was 5.1 approximately 6.3 mcg/ml (mean 5.3 mcg/ml), and values calculated with pharmacokinetic parameters from the mean serum concentration were Tmax = 0.745 hour, Cmax = 5.34 mcg/ml and half life (T1/2) = 89.6 minutes. With 60 minutes intravenous infusion, the peak serum concentration was 6.7 approximately 9.1 mcg/ml (mean 7.5 mcg/ml), and the calculated value was 7.63 mcg/ml. The value after 2 hours was nearly equal to those for intramuscular injection. T 1/2 of beta-phase was 95.8 minutes. With 30 minutes intravenous infusion, the peak serum concentration was 8.4 approximately 11.8 mcg/ml (mean 10.2 mcg/ml), and the calculated value was 9.81 mcg/ml. T 1/2 of beta-phase was 105.3 minutes and the serum concentration of the beta-phase was same as that for intramuscular injection administration after 6 hours. We concluded that 60 minutes intravenous infusion of TOB 90 mg is more effective and safe than the 30 minutes method from the standpoint of toxicity, and the serum concentration of the beta-phase is similar to that with intramuscular injection. With each administration method, urinary recovery was 70 approximately 80% for 8 hours.

[Pharmacokinetic studies of astromicin using a constant-rate continuous intravenous infusion method].

Astromicin (ASTM) was administered intravenously to 4 healthy adult volunteers with an average body weight of 62 kg using a continuous infusion apparatus at a constant rate of 200 mg in 1 hour (Group I), 400 mg in 1 hour (Group II) and 200 mg in 2 hours (Group III). Concentrations of the drug in serum and urine were determined by high power liquid chromatography (HPLC). The mean serum concentration of the 4 subjects reached the peak of 13.32 micrograms/ml in Group I, 22.12 micrograms/ml in Group II and 9.89 micrograms/ml in Group III. The peak concentration was achieved at the end of infusion and was dose-related. After 8 hours, the concentration dropped to less than 1 micrograms/ml in all groups. The urinary recovery rate was 90% in 8 hours and 95% in 24 hours. T1/2 (beta) analyzed by the two-compartment open model was 1.64-1.72 hours. AUC infinity was also dose-related, such as 33.1 micrograms X hr/ml and 31.6 micrograms X hr/ml in Group I and Group III, and 57.6 micrograms X hr/ml in Group II. It is recommended for amikacin (AMK) that the peak serum concentration should not exceed 35 micrograms/ml and the maximum concentration before the next infusion should be less than 5 micrograms/ml. In these experiment, ASTM which is lower in toxicity than AMK did not approach 35 micrograms/ml even at the peak level with the dosage of 400 mg in 1 hour. Furthermore, the excretion of the drug was fast and the serum level of the drug became much lower than 5 micrograms/ml very quickly.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of ribostamycin in healthy volunteers and patients with impaired renal function.

Ribostamycin is an aminoglycoside antibiotic produced by Streptomyces ribosidificus, and extracted and isolated by NIIDA et. al. It has been used widely clinically with its characteristic of low ototoxicity. UMEMURA et al. studied the pharmacokinetics of this antibiotic in animals and reported that it has a similar pharmacokinetic behavior in vivo to kanamycin. In the present studies, the pharmacokinetic behavior of ribostamycin was studied in 5 healthy adult volunteers receiving different doses (0.5 g, 1.0 g and 1.5 g) by intramuscular injection, and 0.5 g by intravenous drip infusion. In addition, a similar study was conducted with 11 patients with varying degrees of renal dysfunction in order to study the application of ribostamycin in such patients.

[Studies on cephradine for intravenous injection (author's transl)].

1) The half-life of serum concentration of cephradine (CED) in patients with normal renal function, was 30 minutes and it prolonged to 83 minutes when combined with probenecid. 2) In the patients with severely impaired renal function, mean serum concentration of CED was 33 mcg/ml 24 hours after 1 g intravenous injection. 3) In clinical observations of 17 cases with infections of lung, urinary tract, and bile duct, the treatment with CED showed excellent results in 5 cases, good in 6, undetermined in 1. No remarkable side effect was observed.