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

Carboplatin disposition was studied in 18 pediatric patients with cancer over a dosage range of 400 to 700 mg/m 2 given on an alternate‐day schedule (total doses of 1200 to 2100 mg/m 2 ) with high‐dose etoposide. Median age was 7.7 years, hepatic functions were normal, and serum creatinine levels were ≤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/m 2 (range, 25.5 to 65.3 ml/min/m 2 ) and a terminal half‐life of 3.6 hours (range, 2.1 to 14.2 hours). Carboplatin clearance (CL) values and volume of distribution (V c ) were highly correlated to body size (CL = 55 × Body surface area in [BSA, in square meters] − 6.7, r 2 = 0.73; V c = 5 × BSA [in square meters] + 0.26, r 2 = 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 ≤960 mg/m 2 ( p < 0.05) but was not influenced by age, gender, or diagnosis. Clinical Pharmacology and Therapeutics (1992) 51 , 701–707; doi: 10.1038/clpt.1992.82