Easy and reliable maximum a posteriori Bayesian estimation of pharmacokinetic parameters with the open‐source R package mapbayr

Bibliographic Details
Title: Easy and reliable maximum a posteriori Bayesian estimation of pharmacokinetic parameters with the open‐source R package mapbayr
Authors: Félicien Le Louedec, Florent Puisset, Fabienne Thomas, Étienne Chatelut, Mélanie White‐Koning
Source: CPT: Pharmacometrics & Systems Pharmacology, Vol 10, Iss 10, Pp 1208-1220 (2021)
Publisher Information: Wiley, 2021.
Publication Year: 2021
Collection: LCC:Therapeutics. Pharmacology
Subject Terms: Therapeutics. Pharmacology, RM1-950
More Details: Abstract Pharmacokinetic (PK) parameter estimation is a critical and complex step in the model‐informed precision dosing (MIPD) approach. The mapbayr package was developed to perform maximum a posteriori Bayesian estimation (MAP‐BE) in R from any population PK model coded in mrgsolve. The performances of mapbayr were assessed using two approaches. First, “test” models with different features were coded, for example, first‐order and zero‐order absorption, lag time, time‐varying covariates, Michaelis–Menten elimination, combined and exponential residual error, parent drug and metabolite, and small or large inter‐individual variability (IIV). A total of 4000 PK profiles (combining single/multiple dosing and rich/sparse sampling) were simulated from each test model, and MAP‐BE of parameters was performed in both mapbayr and NONMEM. Second, a similar procedure was conducted with seven “real” previously published models to compare mapbayr and NONMEM on a PK outcome used in MIPD. For the test models, 98% of mapbayr estimations were identical to those given by NONMEM. Some discordances could be observed when dose‐related parameters were estimated or when models with large IIV were used. The exploration of objective function values suggested that mapbayr might outdo NONMEM in specific cases. For the real models, a concordance close to 100% on PK outcomes was observed. The mapbayr package provides a reliable solution to perform MAP‐BE of PK parameters in R. It also includes functions dedicated to data formatting and reporting and enables the creation of standalone Shiny web applications dedicated to MIPD, whatever the model or the clinical protocol and without additional software other than R.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2163-8306
Relation: https://doaj.org/toc/2163-8306
DOI: 10.1002/psp4.12689
Access URL: https://doaj.org/article/c86571642f3042ac94a9ffd97f1904dc
Accession Number: edsdoj.86571642f3042ac94a9ffd97f1904dc
Database: Directory of Open Access Journals
More Details
ISSN:21638306
DOI:10.1002/psp4.12689
Published in:CPT: Pharmacometrics & Systems Pharmacology
Language:English