Physiologically based pharmacokinetic modeling of tacrolimus for food-drug and CYP3A drug-drug-gene interaction predictions.

ABSTRACT: The immunosuppressant and narrow therapeutic index drug tacrolimus is metabolized mainly via cytochrome P450 (CYP) 3A4 and CYP3A5. For its pharmacokinetics (PK), high inter- and intra-individual variability can be observed. Underlying causes include the effect of food intake on tacrolimus absorption as well as genetic polymorphism in the CYP3A5 gene. Furthermore, tacrolimus is highly susceptible to drug-drug interactions, acting as a victim drug when coadministered with CYP3A perpetrators. This work describes the development of a whole-body physiologically based pharmacokinetic model for tacrolimus as well as its application for investigation and prediction of (i) the impact of food intake on tacrolimus PK (food-drug interactions [FDIs]) and (ii) drug-drug(-gene) interactions (DD[G]Is) inv

SUBMITTER: Loer HLH 

PROVIDER: S-EPMC10196430 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature