Comparative pharmacokinetics of four platinum cytostatics in rats

The time-course of plasma and red blood cells platinum concentration was investigated after the administration of cis-dichlorodiammineplatinum II (cisplatinum), cis-dichlorodiammine-trans-dihydroxyplatinum IV (oxoplatinum), cis-dichloro-trans-dihydroxy-bis-isopropylamine-platinum IV (CHIP) and cis-diammine-1,1-cyclobutanedicarboxylate-platinum II (CBDCA) to male Wistar rats. A physiologically based three-compartment open model was used for pharmacokinetic evaluation. This model provides an estimation of free and protein-bound platinum time-courses from the total platinum species decrease. The total plasma clearance of total platinum increased in the order cisplatinum, CHIP, oxoplatinum and CBDCA. Plasma half-live of gamma-phase, which probably represents the elimination of protein-bound platinum species is similar (51-72 h) in all drugs under study and is longer than that of 131I-HSA (33 h). The platinum concentration in red blood cells shows plateau for all complexes studied at long time intervals and its elimination is very slow.