Population pharmacokinetics of carboplatin in children

Objectives: In pediatric patients, administration of carboplatin according to body surface area results in a large variation in the area under the plasma ultrafilterable carboplatin concentration versus time curve, A population pharmacokinetic study using the NONMEM program was undertaken to determine the effects of a variety of covariates on the clearance of ultrafilterable carboplatin. Patients: Plasma carboplatin pharmacokinetics were determined in 57 children (2 months to 18 years old, with serum creatinine levels ranging from 27 to 268 mu mol/L) treated for various tumor types. Results: The best fit corresponded to the formula: clearance (ml/min) = 2.85 . weight . (1 - 0.00357 . serum creatinine) . (1 - 0.372 . Np) + 8.7 (with serum creatinine in micromoles per liter, weight in kilograms, and Np = 1 or 0 for unilateral nephrectomy or not, respectively). The interindividual variability in clearance, as expressed by the coefficient of variation, decreased from 74% (no covariates) to 49% by taking account of weight, and to 29% under the final regression formula. Conclusion: The ability of this formula to predict carboplatin clearance in children should be evaluated prospectively and compared to a method based on the determination of the glomerular filtrationrate.