J Pharm Sci
Pharmacokinetics of cisplatin and its monohydrated complex in humans.   
ABSTRACT
The pharmacokinetics of cisplatin and its cytotoxic hydrolysis product cis-diammineaquachloroplatinum(II) ion (monohydrated complex) were investigated in seven patients after they received a 1-h infusion of cisplatin in normal saline at 100 mg/m2. The concentrations of intact cisplatin and the monohydrated complex were determined in blood by liquid chromatography with post-column derivatization, using diethyldithiocarbamate as the reagent. A pharmacokinetic model was developed assuming that a fraction of the dose (2.3%) is present as the monohydrated complex in the infusion solution and that reversible reactions between cisplatin and its monohydrated complex prevail. The clearances of cisplatin and the monohydrated complex were 0.32 +/- 0.05 and 0.27 +/- 0.11 L/min/m2, respectively. The apparent volume of distribution was considerably smaller for the monohydrated complex (4 +/- 2 L/m2) than for cisplatin (11 +/- 2 L/m2). The elimination rate constants were 0.030 +/- 0.002 and 0.07 +/- 0.02 min-1 for cisplatin and the monohydrated complex, respectively. The area under the time-concentration curve for the monohydrated complex was approximately 15% of that for cisplatin. It is concluded that the significant amounts of the monohydrated complex present in blood are due to the fraction already present in the administered dose and to the fraction formed in blood.

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