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Population pharmacokinetics of carboplatin in children
Author(s) -
Chatelut Etienne,
Boddy Alan V.,
Peng Bin,
Rubie Hervé,
Lavit Michel,
Dezeuze Annik,
Pearson Andrew D. J.,
Roché Henri,
Robert Alain,
Newell David R.,
Canal Pierre
Publication year - 1996
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(96)90113-7
Subject(s) - carboplatin , pharmacokinetics , nonmem , medicine , renal function , creatinine , urology , population , body surface area , population pharmacokinetics , plasma clearance , coefficient of variation , body weight , endocrinology , chemotherapy , chemistry , environmental health , chromatography , cisplatin
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 μmol/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. Clinical Pharmacology & Therapeutics (1996) 59 , 436–443; doi: