Premium
Pharmacokinetic scaling of SJ‐8029, a novel anticancer agent possessing microtubule and topoisomerase inhibiting activities, by species‐invariant time methods
Author(s) -
Shin Beom S.,
Kim Dong H.,
Cho Chang Y.,
Park Si K.,
Chung Sun G.,
Cho Eui H.,
Lee Sun H.,
Joo Jeong H.,
Kwon Ho S.,
Lee Kang C.,
Yoo Sun D.
Publication year - 2003
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.352
Subject(s) - pharmacokinetics , topoisomerase , pharmacology , microtubule , animal species , allometry , chemistry , enzyme , stereochemistry , biology , biochemistry , zoology , ecology , microbiology and biotechnology
Abstract This study examined the pharmacokinetic disposition of SJ‐8029, a novel anticancer agent possessing microtubule and topoisomerase inhibiting activities, in mice, rats, rabbits and dogs after i.v. administration. The serum concentration ‐ time curves of SJ‐8029 were best described by tri‐exponential equations in all these animal species. The mean Cl , V ss and t 1/2 were 0.3 l/h, 0.1 l and 63.2 min in mice, 1.5 l/h, 1.6 l and 247.7 min in rats, 13.8 l/h, 39.6 l and 245.9 min in rabbits, and 29.2 l/h, 44.6 l and 117.4 min in dogs, respectively. Based on animal data, the pharmacokinetics of SJ‐8029 were predicted in humans using simple allometry and also by several species‐invariant time transformations using kallynochron, apolysichron and dienetichron times. The human pharmacokinetic parameters of Cl , V ss and t 1/2 predicted by the simple allometry and various species‐invariant time methods were 50.4–145.0 l/h, 369.0–579.8 l and 242.0–1448.3 min, respectively. These preliminary parameter values may be useful in designing early pharmacokinetic studies of SJ‐8029 in humans. Copyright © 2003 John Wiley & Sons, Ltd.