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

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, 0.1l and 63.2min 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, 369.0-579.81 and 242.0-1448.3 min, respectively. These preliminary parameter values may be useful in designing early pharmacokinetic studies of SJ-8029 in humans.