PHARMACOKINETICS OF CISPLATIN AND ITS MONOHYDRATED COMPLEX IN HUMANS

The pharmacokinetics of cisplatin and its cytotoxic hydrolysis product cis-diammineaquachloroplatinum(II) ion (monohydrated complex) were in vestigated in seven patients after they received a 1-h infusion of cis platin in normal saline at 100 mg/m(2). The concentrations of intact c isplatin and the monohydrated complex were determined in blood by liqu id chromatography with post-column derivatization, using diethyldithio carbamate as the reagent. A pharmacokinetic model was developed assumi ng thai a fraction of the dose (2.3%) is present as the monohydrated c omplex in the infusion solution and that reversible reactions between cisplatin and its monohydrated complex prevail. The clearances of cisp latin and the monohydrated complex were 0.32 +/- 0.05 and 0.27 +/- 0.1 1 L/min/m(2), respectively. The apparent volume of distribution was co nsiderably smaller for the monohydrated complex (4 +/- 2 L/m(2)) than for cisplatin (11 +/- 2 L/m(2)). The elimination rate constants were 0 .030 +/- 0.002 and 0.07 +/- 0.02 min(-1) for cisplatin and the monohyd rated complex, respectively. The area under the time-concentration cur ve for the monohydrated complex was similar to 15% of that for cisplat in. It is concluded that the significant amounts of the monohydrated c omplex present in blood are due to the fraction already present in the administered dose and to the fraction formed in blood.