In vitro plasma binding of some second generation antitumor platinum complexes.

The kinetics of five cisplatin analogs binding to human plasma fractions possessing a molecular weight greater than 50,000 daltons were studied. Each drug solution in plasma ultrafiltrate or phosphate buffer (pH = 7.4, mu = 0.154) was mixed with human plasma and filterable platinum concentrations were measured versus time by atomic absorption spectrophotometry. The only Pt IV compound studied did not bind. All the other Pt II complexes bound, but their binding kinetics were quite different. The experimental data were fitted to a theoretical equation based on the hypothesis that plasma nucleophilic agents possessing a molecular weight greater than 50,000 daltons are able to react with Pt compounds with an apparent second order rate constant. The apparent reaction rate constants and initial concentrations of these nucleophilic agents were calculated. The difference between the respective values obtained for each cisplatin analog could be explained by differences in their chemical formulas. Therefore our result should contribute towards a better understanding of the pharmacokinetics of the cisplatin analogs studied.