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Population pharmacokinetics of carboplatin in children

Lookup NU author(s): Professor Alan Boddy, Professor Andrew Pearson, Professor Herbie Newell


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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.

Publication metadata

Author(s): Chatelut, E., Boddy, A. V., Peng, B., Rubie, H., Lavit, M., Dezeuze, A., Pearson, A. D. J., Roche, H., Robert, A., Newell, D. R., Canal, P.

Publication type: Article

Publication status: Published

Journal: Clinical Pharmacology and Therapeutics

Year: 1996

Volume: 59

Issue: 4

Pages: 436-443

Print publication date: 31/03/1996

ISSN (print): 0009-9236

ISSN (electronic): 1532-6535


DOI: 10.1016/S0009-9236(96)90113-7


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