Pharmacokinetics of Unchanged Carboplatin (CBDCA) in Patients with Small Cell Lung Carcinoma

The disposition of the cisplatin analogue carboplatin was studied in seven patients with small cell lung cancer. Carboplatin 100 mg/m2 was administered without hydration by a 1-h infusion with VP16-213 120 mg/m2 on days 1, 2 and 3 of each course. Plasma and urine collections were made on days 1 and 3 of the first course of treatment. Carboplatin levels in plasma ultrafiltrate and urine were quantitated using a specific and sensitive, high-performance liquid chromatographic assay which involved sample clean-up on a Dowex-2 column prior to injection. Estimates of pharmacokinetic parameters determined using either compartmental or non-compartmental methods were comparable. There was no difference between carboplatin pharmacokinetic parameters determined on days 1 and 3 of treatment. The mean (+/- SD) carboplatin half-life determined from plasma data on day 1 was 105 +/- 30.4 min and was not significantly different from that determined using urinary excretion rate data (107 +/- 51.7 min). Urinary excretion rate plots showed that carboplatin elimination was mono-exponential for up to 14 h after infusion. Total-body clearance was 105 +/- 40.0 ml min-1 m-2, renal clearance 64.3 +/- 44.1 ml min-1 m-2, and volume of distribution 17.3 +/- 4.2 l/m2 on the 1st day of treatment. Of the administered dose, 58.4% +/- 21.2% was recovered in urine over a 24-h period after the start of the infusion. The mean renal clearance of carboplatin was comparable to creatinine clearance. Carboplatin disposition was clearly defined in the patients studied using analytical methodology specific for the unchanged drug.