Preclinical Pharmacokinetics of C118P, a Novel Prodrug of Microtubules Inhibitor and Its Metabolite C118 in Mice, Rats, and Dogs.

ABSTRACT: C118P, a phosphate prodrug of C118, which is a novel microtubule protein inhibitor, is currently under Phase I clinical development in China for treating ovarian cancer and lung cancer. The preclinical pharmacokinetics of prodrug C118P and its metabolite C118 were extensively characterized in vivo in mice, rats, and dogs and in vitro to support the further development of C118P. The preclinical tissue distribution and excretion were investigated in rats. Plasma protein binding in mice, rat, and human, and hepatic microsomal metabolic stability in mice, rat, dog, monkey, and human, were also evaluated. The (AUC_0-inf) and C_30s of C118P at 50 mg/kg in rats and 6 mg/kg in dogs, and the C_2min of C118 at 6 mg/kg in dogs increased less than the dosage increase, sug

SUBMITTER: Zhang C 

PROVIDER: S-EPMC6278385 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature