Comparative pharmacokinetics of Sch 28191 and amphotericin B in mice, rats, dogs, and cynomolgus monkeys

Author:

Kim H,Loebenberg D,Marco A,Symchowicz S,Lin C

Abstract

The pharmacokinetics of Sch 28191, the N-D-ornithyl methyl ester of amphotericin B, and amphotericin B were studied in mice, rats, dogs, and cynomolgus monkeys after an intravenous dose of 0.6 mg/kg was administered. The decline in the concentrations of Sch 28191 and amphotericin B in serum appeared to be biphasic in nature. The half-life at the distribution phase and the half-life at the elimination phase of Sch 28191 were similar to those of amphotericin B in all animals studied. The half-life at the distribution phase in serum was 0.9 to 1.5 h in all animals studied. The half-lives at the elimination phase in serum were 25 to 28 h in mice, 16 to 18 h in rats, 44 to 47 h in dogs, and 35 h in cynomolgus monkeys. The areas under the serum concentration-time curves of Sch 28191 were five- to eightfold larger than those of amphotericin B in rats, dogs, and cynomolgus monkeys but were only slightly larger than those of amphotericin B in mice. In dogs, the urinary excretion (over 9 days) of unchanged drug accounted for 23% of the Sch 28191 dose and 25% of the amphotericin B dose. The concentrations of Sch 28191 in serum were also studied after the intravenous administration of 0.3, 0.6, or 1.25 mg/kg to dogs. The serum concentration-time curves were parallel for these doses. There was a linear relationship between the areas under the concentration-time curves and the doses, indicating dose proportionality.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference7 articles.

1. Atkinson A. J. and J. E. Bennett. 1978. Amphotericin B pharmacokinetics in humans. Antimicrob. Agents Chemother.

2. Bennett J. D. 1976. Amphotericin B binding to serum betalipoprotein p. 107-109. In K. Iwata (ed.) Recent advances in medical and veterinary mycology. University of Tokyo Press Tokyo Japan.

3. A pharmacological guide to the clinical use of amphotericin B;Bindschadler D. D.;J. Infect. Dis.,1969

4. Excretion pathways of amphotericin B;Craven P. C.;J. Infect. Dis.,1979

5. Comparative pharmacology of amphotericin B and amphotericin B methyl ester in the non-human primate, Macaca mulatta;Jagdis F. A.;Antimicrob. Agents Chemother.,1977

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