Population pharmacokinetics of high-dose carboplatin in children and adults

Therapeutic Drug Monitoring
Andreas LindauerUlrich Jaehde

Abstract

Although for conventional dosing of carboplatin, several strategies are available to individualize the dose based on renal function measurements, such approaches are still rare for high-dose regimens with autologous stem cell support. The purpose of this study was to investigate the influence of patient- and regimen-specific factors on the pharmacokinetics of carboplatin and to compare the performance of different dose individualization strategies (Calvert, Newell, Chatelut, flat dosing, dosing according to body surface area). A combined data set with 69 patients from five studies, including 13 pediatric patients, was subject to a population pharmacokinetic analysis using NONMEM. The covariate analysis revealed that carboplatin clearance after high-dose chemotherapy was highly related to creatinine clearance, body height, and infusion duration. After inclusion of these covariates, the population parameter variability of clearance decreased from 53% in the base model to 21% in the final model. We also developed an alternative model that related body weight, instead of height, to clearance by means of allometric scaling. An evaluation of the predictive performance of existing a priori dose individualization strategies revealed th...Continue Reading

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Citations

Dec 12, 2012·British Journal of Clinical Pharmacology·Johan G C van HasseltAlwin D R Huitema
Nov 4, 2015·Basic & Clinical Pharmacology & Toxicology·Himanshu NaikJohan Areberg
Jun 11, 2017·The Journal of Pharmacology and Experimental Therapeutics·Andrea HenrichZinnia Patricia Parra-Guillen

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