The pharmacokinetics of high-dose carboplatin in pediatric patients with cancer

Abstract

Carboplatin disposition was studied in 18 pediatric patients with cancer over a dosage range of 400 to 700 mg/m2 given on an alternate-day schedule (total doses of 1200 to 2100 mg/m2) with high-dose etoposide. Median age was 7.7 years, hepatic functions were normal, and serum creatinine levels were less than or equal to 1.0 mg/dl. Carboplatin pharmacokinetics were determined by atomic absorption spectroscopy. Median pharmacokinetic parameters for ultrafilterable platinum were as follows: clearance 45.8 ml/min/m2 (range, 25.5 to 65.3 ml/min/m2) and a terminal half-life of 3.6 hours (range, 2.1 to 14.2 hours). Carboplatin clearance (CL) values and volume of distribution (VC) were highly correlated to body size (CL = 55 x Body surface area in [BSA, in square meters] - 6.7, r2 = 0.73; VC = 5 x BSA [in square meters] + 0.26, r2 = 0.69). However, carboplatin doses normalized to BSA still resulted in twofold to threefold variability in area under the concentration-time curve. Carboplatin CL was significantly lower in those subjects (n = 9) who had previously received cumulative cisplatin doses of greater than or equal to 960 mg/m2 (p less than 0.05) but was not influenced by age, gender, or diagnosis.