Comparative pharmacokinetics and interspecies scaling of amphotericin B in several mammalian species

Athiwat Hutchaleelaha, Hsiao Hui Chow, Michael Mayersohn

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

This study employed several interspecies scaling methods, to evaluate the applicability of extrapolating to man, pharmacokinetic information obtained from animals for amphotericin B, an anti-fungal drug. Pharmacokinetic parameters from four animal species (mouse, rat, monkey and dog) and man were obtained from the literature or from analysis of data reported in the literature. The allometric relationships (obtained from four animal species) as a function of species body weight (W; kg) for systemic clearance per maximum life span potential (CL(S)/MLP), steady-state volume of distribution (V(SS)), apparent volume of distribution (V(β)) and volume of the central compartment (V(C)) were: 5691W1.096; 2.46W0.839; 3.08W0.948 and 1.07W0.965 respectively. The allometric relationships for half-life (h) and mean residence time (h) did not scale well with body weight. The prediction of pharmacokinetic parameters in man from the allometric equations do not always agree with those reported in the literature which are based upon a limited number of studies with few human subjects. The plasma concentration-time profiles from these animals were adjusted by normalizing the concentration with dose/W0.948, and re-plotted on different pharmacokinetic time scales. The syndesichrons plot produced an almost superimposable profile of adjusted concentrations as a function of adjusted time among the four species.

Original languageEnglish (US)
Pages (from-to)178-183
Number of pages6
JournalJournal of Pharmacy and Pharmacology
Volume49
Issue number2
DOIs
StatePublished - Feb 1997

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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