Disposition of unchanged cisplatin in patients with ovarian cancer

The disposition of cisplatin (cis-diamminedichloroplatinum II) was studied in the first course of treatment in seven patients (56 +/- 12 years) with ovarian carcinoma by analytic methodology specific for the unchanged drug. Particular attention was paid to rapid blood and urine sample processing to avoid drug losses. Patients were catheterized for urine collections. During and after infusion, plasma levels of unbound cisplatin were simultaneously fitted to a one-compartment model. Creatinine clearance was determined at the same time as cisplatin renal clearance and was 38 +/- 16 ml/min/m2. Total clearance of unbound cisplatin was 253 +/- 48 ml/min/m2 and volume of distribution was 11.5 +/- 2.7 L/m2. Cisplatin half-life was similar when determined from plasma (31.6 +/- 6.0 minutes) or urinary excretion rate data (24.4 +/- 4.0 minutes). Urinary excretion of unchanged drug was 23.3% +/- 8.6% of the dose and renal clearance 56.9 +/- 18.0 ml/min/m2. Renal clearance exceeded creatinine clearance in all patients ratio = 1.9 +/- 1.2), confirming previous suggestions of active renal tubular secretion of cisplatin. Renal clearance was nonlinear with time in two of the patients who received the 2-hour infusion, possibly reflecting changing renal tubular reabsorption. Pharmacokinetic studies of unchanged cisplatin rather than total platinum are therefore practical and could be pursued in further studies defining cisplatin disposition in patients.