Inhibition of T-cell activation and proliferation by mycophenolic acid in patients awaiting liver transplantation: PK/PD relationships. - Archive ouverte HAL Access content directly
Journal Articles Pharmacological Research Year : 2011

Inhibition of T-cell activation and proliferation by mycophenolic acid in patients awaiting liver transplantation: PK/PD relationships.

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Abstract

Mycophenolic acid (MPA) plasma concentrations were reported to be associated with a decrease in T-cell proliferation, and in both IL-2 α-chain (CD25) and transferin receptor (CD71) expression. The aim of this study was to confirm, quantify and model these PK/PD relationships. Full profiles of MPA plasma concentrations, T-cell proliferation, intracytoplasmic IL-2 and TNF-α expression, and both CD71 and CD25 expression were collected over the 12h after dosing in 10 patients on the waiting list for liver transplantation. Data were analyzed using NONMEM(®). Both CD25 and CD71 expression and T cell proliferation clearly decreased (median of decrease from baseline 62%, 68% and 94%, respectively) with increasing MPA concentrations, in contrast to IL-2 and TNF-α expression. The CD25 and CD71 baseline expression (E(0)) and maximum effect (E(max)) were correlated with the E(0) and E(max) values of T-cell proliferation (r(2)=0.509 and r(2)=0.622, respectively). The CD25, CD71 expression and T-cell proliferation profiles were adequately fitted using a sigmoid inhibitory E(max) model. Low estimated values (≤2 mg/L) for 50% inhibitory MPA concentrations were obtained. This study confirmed a transient MPA concentration-dependent decrease in T-cells expressing CD25 and CD71 and a strong reduction of T-cell proliferation and showed that CD25 and CD71 expression was correlated with T-cell proliferation.
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Dates and versions

inserm-00926481 , version 1 (09-01-2014)

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Aurélie Prémaud, Annick Rousseau, Gyasi Johnson, Cindy Canivet, Peggy Gandia, et al.. Inhibition of T-cell activation and proliferation by mycophenolic acid in patients awaiting liver transplantation: PK/PD relationships.. Pharmacological Research, 2011, 63 (5), pp.432-8. ⟨10.1016/j.phrs.2011.01.005⟩. ⟨inserm-00926481⟩
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