Physiologically Based Pharmacokinetic Modelling to Identify Physiological and Drug Parameters Driving Pharmacokinetics in Obese Individuals.

ABSTRACT: Obese individuals are often underrepresented in clinical trials, leading to a lack of dosing guidance. This study aimed to investigate which physiological parameters and drug properties determine drug disposition changes in obese using our physiologically based pharmacokinetic (PBPK) framework, informed with obese population characteristics. Simulations were performed for ten drugs with clinical data in obese (i.e., midazolam, triazolam, caffeine, chlorzoxazone, acetaminophen, lorazepam, propranolol, amikacin, tobramycin, and glimepiride). PBPK drug models were developed and verified first against clinical data in non-obese (body mass index (BMI) ≤ 30 kg/m2) and subsequently in obese (BMI ≥ 30 kg/m2) without changing any drug parameters. Additionally, the PBPK model was used to study the e

SUBMITTER: Berton M 

PROVIDER: S-EPMC9998327 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature