title: Maximum a posteriori bayesian estimation of mycophenolic acid pharmacokinetics in renal transplant recipients at different postgrafting periods.
abstract: The aim of this study was to develop maximum a posteriori probability (MAP) Bayesian estimators of mycophenolic acid (MPA) pharmacokinetics (PK) capable of accurately estimating the MPA interdose AUC in renal transplant patients using a limited number of blood samples. The individual MPA plasma concentration-time profiles of 44 adult kidney transplant recipients were retrospectively studied: in 24 de novo transplant patients, 2 profiles were obtained on day 7 and day 30 after transplantation, and in 20 stable transplant patients, 1 profile was obtained in the stable period (>3 months). MPA was assayed by liquid chromatography-mass spectrometry. Concentration data were fitted using previously designed PK models, including 1 or 2Gamma-distribution to describe the absorption rate. MAP-Bayesian estimations were performed using an in-house program. For each posttransplantation period, the limited sampling strategies (LSS) providing either the best determination coefficient or the lowest bias for AUC estimates with respect to trapezoidal AUCs were selected and compared with respect to the percentage of "clinically acceptable" AUC estimates (ie, within -20% to +20% of the true value) they yielded. A common LSS (blood samples collected at T20 min, T1 h, and T3 h postdosing), convenient for all 3 periods, was also selected and validated: bias (RMSE%) values were -5.7% (20.5%), -8.2% (14.4%), and +0.4% (12.0%) on D7, D30, and for >M3 with respect to the reference values obtained using the trapezoidal rule, respectively. For the first time, MAP-Bayesian estimators of MPA systemic exposure at different posttransplantation periods (early as well as later periods) could be designed. They have since been used for MPA dose adaptation in concentration-controlled studies as well as for MPA therapeutic drug monitoring in clinical practice.
authors.affiliation: Department of Pharmacology-Toxicology, University Hospital, Limoges, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Prémaud
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Meur
authors.forename: Jean
authors.initials: J
authors.lastname: Debord
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Szelag
authors.forename: Annick
authors.initials: A
authors.lastname: Rousseau
authors.forename: Guillaume
authors.initials: G
authors.lastname: Hoizey
authors.forename: Olivier
authors.initials: O
authors.lastname: Toupance
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
mesh_terms: D019540:Area Under Curve; D001499:Bayes Theorem; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000493:pharmacokinetics*; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid