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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 1/2002

01-01-2002 | Original Research Article

Maximum A Posteriori Bayesian Estimation of Oral Cyclosporin Pharmacokinetics in Patients with Stable Renal Transplants

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

Published in: Clinical Pharmacokinetics | Issue 1/2002

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Abstract

Objective

To develop a maximum a posteriori probability (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.

Patients

20 adult patients with stable renal transplants given orally administered microemulsified cyclosporin and mycophenolate.

Methods

Cyclosporin 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 results

MAP 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 AUC12 and Cmax, respectively.

Conclusion

This paper reports preliminary results in a stable renal transplant patient population, showing that MAP Bayesian estimation can allow accurate prediction of AUC12 and Cmax with 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.
Footnotes
1
Use of tradenames is for product identification only, and does not imply endorsement.
 
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Metadata
Title
Maximum A Posteriori Bayesian Estimation of Oral Cyclosporin Pharmacokinetics in Patients with Stable Renal Transplants
Authors
Frédéric Leger
Jean Debord
Yann Le Meur
Annick Rousseau
Mathias Büchler
Gérard Lachâtre
Gilles Paintaud
Professor Pierre Marquet
Publication date
01-01-2002
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 1/2002
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200241010-00006

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