Busulfan and cycosporin in bone graft children

Annales pharmaceutiques françaises
V BertolleG Aulagner

Abstract

Most drugs exhibit both inter- and intra-individual pharmacokinetic and pharmacodynamic variability. This variability explains the different responses observed in patients exposed to standard doses and must be taken into consideration when the therapeutic window is narrow. Population pharmacokinetics provides mean (or median) values of pharmacokinetic parameters as well as the distribution pattern and the statistical relationship with covariables in a group of individuals presenting common characteristics. Among the different methods developed for population pharmacokinetics, the data pool method, as well as the two-step and one-step methods (NONMEM and NPEM) are attractive. Population models can then be developed using bayesian logistics to obtain an estimation of the pharmacokinetic parameters of a given patient and predict the most adapted dose in light of the therapeutic target (residual serum concentration, mean concentration.). Busulfan is an alkylizing agent used instead of radiotherapy for pre-graft preparation before bone marrow grafts in children. This compound requires dose monitoring because of its narrow therapeutic window: under-dosing raises the risk of graft rejection; inversely over-dosing can cause potentially...Continue Reading

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