Atypical pharmacokinetics and excretion of new platinum analogues in rodents

Abstract

Purpose: Two new series of platinum complexes with cytotoxic activity in vivo are [Pt(NRCH2)2 L2], (R = polyfluorophenyl, L = pyridine or substituted pyridine) and [Pt(NRCH2CH2NR′2)2L(X)], (R, L as before; R′ = Me or Et, X = halogen). The aim of this study was to determine the pharmacokinetics and excretion in mice and in isolated perfused rat livers of a representative compound from each class, respectively: Ptl03 (R = p-HC6F4, L = pyridine) and Ptl09 (R, L as for Ptl03, R′ = Et, X = I). Methods: Mice were given intraperitoneal injections of active doses of Ptl03, Ptl09, or cisplatin in a variety of vehicles. Blood was sampled at several times to 48 h. Some mice were placed in metabolic cag..