Model independent pharmacokinetic study of cis-dichlorodiammineplatinum (II)

The disposition of cis-dichlorodiammineplatinum (CDDP) was evaluated in 8 patients with cancer. They received 80 mg/m2 of CDDP as a 20 min i.v. infusion. Sixteen blood samples and sixteen urine samples were obtained over 6 hours following the completion of cis-platinum infusion and were assayed for total platinum by flameless atomic absorption spectrometry. There was a great variation among maxima urinary concentrations (123 to 1436 mumol . l-1) and an important decrease of diuresis appeared 3 hours after the infusion. Model independent pharmacokinetic parameters: distribution volume and renal elimination clearance were determined. The calculated distribution volumes suggest an extremely rapid diffusion of CDDP into the peripheral compartment. The ratio of total platinum clearance to creatinine clearance decreased 75 min after infusion, this being the consequence of the variation of protein binding or nephrotoxicity.