首页   按字顺浏览 期刊浏览 卷期浏览 Maximum A Posteriori Bayesian Estimation of Oral Cyclosporin Pharmacokinetics in Patien...
Maximum A Posteriori Bayesian Estimation of Oral Cyclosporin Pharmacokinetics in Patients with Stable Renal Transplants

 

作者: Frédéric Leger,   Jean Debord,   Yann Le Meur,   Annick Rousseau,   Mathias Büchler,   Gérard Lachâtre,   Gilles Paintaud,   Pierre Marquet,  

 

期刊: Clinical Pharmacokinetics  (ADIS Available online 2002)
卷期: Volume 41, issue 1  

页码: 71-80

 

ISSN:0312-5963

 

年代: 2002

 

出版商: ADIS

 

关键词: Cyclosporin modified, pharmacokinetics

 

数据来源: ADIS

 

摘要:

ObjectiveTo develop a maximuma posterioriprobability (MAP) Bayesian estimator for the pharmacokinetics of oral cyclosporin, based on only three timepoints, and evaluate its performance with respect to a full-profile nonlinear regression approach.Patients20 adult patients with stable renal transplants given orally administered microemulsified cyclosporin and mycophenolate.MethodsCyclosporin was assayed by liquid chromatography-mass spectrometry. Nonlinear regression and MAP Bayesian estimation were performed using a home-made program and a previously designed pharmacokinetic model including an S-shaped absorption profile described by a gamma distribution.Outcome measures and resultsMAP Bayesian estimation using the best limited sampling strategy (before administration, and 1 and 3 hours after administration) was compared with nonlinear regression (taken as the reference method) for the prediction of the different pharmacokinetic parameters and exposure indices. Median relative prediction error was −0.49 and −3.42% for area under the concentration-time curve over the administration interval of 12 hours (AUC12) and estimated peak drug concentration (Cmax), respectively (nonsignificant). Relative precision was 2.00 and 4.32%, and correlation coefficient (r) was 0.985 and 0.955, for AUC12and Cmax, respectively.ConclusionThis paper reports preliminary results in a stable renal transplant patient population, showing that MAP Bayesian estimation can allow accurate prediction of AUC12and Cmaxwith only three samples (0, 1 and 3 hours). Although these results require confirmation by further studies in other clinical settings, using other drug combinations, other analytical methods and commercially available pharmacokinetic software, the method seems promising as a tool for the therapeutic drug monitoring of cyclosporin in clinical practice or for exposure-controlled studies.

 

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