Pharmacokinetics of ribostamycin in paediatric patients.

In the present study, ribostamycin concentrations in serum were measured by microbiological assay in 20 paediatric patients aged 3 months to 11 years after intramuscular ribostamycin 10, 15 and 20 mg/kg. All pharmacokinetic parameters and statistical analyses were calculated by computer. These results showed that the absorption rate constant (ka), elimination rate constant (ke), time to peak serum concentration (tmax), elimination half-life (t1/2), apparent volume of distribution (Vd/F), total body clearance (CL) and area under the serum concentration-time curve (AUC) were significantly different in infants under 6 months from those in children over 3 years (p less than 0.05), except for the peak serum concentration (Cmax) and lag time from administration to the first appearance of drug in the serum (tlag) [p greater than 0.05]. The absorption of ribostamycin in infants was more rapid than that in children, but elimination was slower (p less than 0.05). The Vd/F and CL in infants were also larger than in children (p less than 0.01). There were significant positive correlations between Cmax, AUC and ribostamycin dosage (p less than 0.01). Pharmacokinetic parameters for infants and children were compared with those observed in adults, and it was found that ribostamycin absorption and elimination were more rapid in the paediatric patients. The Cmax in children and infants after intramuscular ribostamycin 10 mg/kg approached that in adults after an intramuscular dose of ribostamycin 500mg. Using a 1-compartment open pharmacokinetic model, the optimum intramuscular ribostamycin administration interval was estimated as 6.01 and 7.56h for children and infants, respectively, while the value was 8.5h in adults. When the drug was administered in multiple doses of 15 mg/kg intramuscularly every 8h, no accumulation occurred in children. It is suggested that ribostamycin be administered in intramuscular doses of 10 to 15 mg/kg twice daily in infants and 3 times daily in children, respectively.

Analysis of the phamacokinetics of ribostamycin in serum and perilymph of guinea pigs after single and multiple doses.

The pharmacokinetics of ribostamycin in serum and perilymph of guinea pigs was studied after a single s.c. injection of 400 mg/kg or 14 daily injections of the same dose. The repetitive administration of ribostamycin did not produce functional impairment of the kidney and ototoxicity was slight. The pharmacokinetic data were analysed by non-linear least mean squares regression. Ribostamycin did not accumulate in either serum or perilymph after multiple dosing. The half-life of the drug in perilymph was 15.8 h after a single injection, but 7.6 h after the last of 14 injections. The area under the ribostamycin concentration in perilymph against time curve was also reduced after multiple dosing. These changes were found to be due to a marked increase in the rate of transfer of the drug from perilymph to serum after multiple dosing.

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.