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Killing several birds with one stone: A multi-indication population pharmacokinetic model and Bayesian estimator for

Yeleen Fromage1, Hamza Sayadi1, Kevin Koloskoff2,3

  • 1Department of Pharmacology, Toxicology and Pharmacovigilance, CHU de Limoges, Limoges, France.

British Journal of Clinical Pharmacology
|December 22, 2024
PubMed
Abstract

Insights

This study developed a population pharmacokinetic model for mycophenolic acid (MPA) using a limited sampling strategy. The model accurately estimates MPA AUC for personalized dosing in transplant and autoimmune disease patients.

Area of Science:

  • Pharmacokinetics
  • Drug Metabolism and Disposition
  • Clinical Pharmacology

Background:

  • Mycophenolic acid (MPA) pharmacokinetics are highly variable.
  • Existing population pharmacokinetic (popPK) models for MPA are limited, especially for estimating AUC in specific patient populations.
  • Enteric-coated mycophenolate sodium (EC-MPS) is widely used but requires precise dosing due to variable MPA levels.

Purpose of the Study:

  • To develop a popPK model for MPA.
  • To create a Bayesian estimation (MAP-BE) method for MPA AUC using a limited sampling strategy (LSS).
  • To validate the model and LSS in solid organ transplant (SOT), hematopoietic stem cell (HSC), and autoimmune disease (AID) patients.

Main Methods:

  • PK profiles were extracted and split into development and validation sets.
  • A one-compartment model with double-gamma absorption was selected using the SAEM algorithm.
  • MAP-BE and LSS were used to predict MPA AUC and compared against reference values.

Main Results:

  • A one-compartment model with double-gamma absorption and first-order elimination best described MPA PK.
  • The optimal LSS included samples at 20 min, 2 h, and 4 h post-dose.
  • The LSS demonstrated good performance in validation sets with low prediction error (rMPE -2.67% to -4.91%) and RMSE (13.55% to 13.47%).

Conclusions:

  • The developed double-gamma absorption model accurately fits MPA PK data.
  • The MAP-BE with LSS provides a reliable tool for individualizing EC-MPS (MPA) dosage.
  • This approach supports optimized MPA dosing in SOT, HSC, and AID patients.
Keywords:
MAP‐BEhaematopoietic stem cell recipientsmycophenolate sodiumpopulation pharmacokineticssolid organ transplantation

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