Pharmacokinetic scaling of SJ-8029, a novel anticancer agent possessing microtubule and topoisomerase inhibiting activities, by species-invariant time methods

✍ Scribed by Beom S. Shin; Dong H. Kim; Chang Y. Cho; Si K. Park; Sun G. Chung; Eui H. Cho; Sun H. Lee; Jeong H. Joo; Ho S. Kwon; Kang C. Lee; Sun D. Yoo

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 113 KB
• Volume: 24
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.352

✦ Synopsis

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.