Pharmacokinetics of mycophenolic acid administered 3 times daily after hematopoietic stem cell transplantation with reduced-intensity regimen.

Abstract : Mycophenolate mofetil (MMF) is an immunosuppressive drug used as a prophylactic agent to prevent acute graft-versus-host disease (aGVHD) after hematopoietic stem cell transplantation (HSCT). After reduced-intensity conditioning (RIC) regimen, administration of MMF orally 3 times a day (tid) seems to be more beneficial than twice a day (bid). However, information regarding the pharmacokinetic (PK) parameters of mycophenolic acid (MPA), the active metabolite of MMF, administered in this regimen are very limited. We performed a prospective study in 15 patients for whom 3 sets of sampling were performed: at the beginning of the treatment, after 1 week, and after 1 month. Two consecutive 8-hour sets of sampling were performed at day 0 (D0) and D7. Plasma concentrations of MPA were quantified and areas under the curve for 8hours (AUC(0-8)), and maximal and through concentrations were calculated. The results show that AUC(0-8) increases between the beginning of treatment and the end of the first week, but remains stable thereafter. Moreover, a trend to lower AUC(0-8) was observed for the patients who experienced GVHD > or =2 compared to those patients who did not. The other PK parameters are not associated with pharmacodynamic events. A limited sampling strategy with Bayesian estimators is currently under investigation to confirm these data and the role of D7 AUC(0-8) as a potential target of therapeutic drug monitoring (TDM).
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Biology of Blood and Marrow Transplantation, Elsevier, 2009, 15 (9), pp.1134-9. 〈10.1016/j.bbmt.2009.04.011〉
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Soumis le : mardi 18 mai 2010 - 12:11:09
Dernière modification le : lundi 9 juillet 2018 - 13:12:02

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Bernard Royer, Fabrice Larosa, Faezeh Legrand, Pauline Gerritsen-Van Schieveen, Michel Bérard, et al.. Pharmacokinetics of mycophenolic acid administered 3 times daily after hematopoietic stem cell transplantation with reduced-intensity regimen.. Biology of Blood and Marrow Transplantation, Elsevier, 2009, 15 (9), pp.1134-9. 〈10.1016/j.bbmt.2009.04.011〉. 〈inserm-00484323〉

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