A Theoretical Physiologically-Based Pharmacokinetic Approach to Ascertain Covariates Explaining the Large Interpatient Variability in Tacrolimus Disposition.

ABSTRACT: Physiologically-based pharmacokinetic (PBPK) modeling allows assessment of the covariates contributing to the large pharmacokinetic (PK) variability of tacrolimus; these include multiple physiological and biochemical differences among patients. A PBPK model of tacrolimus was developed, including a virtual population with physiological parameter distributions reflecting renal transplant patients. The ratios of predicted to observed dose-normalized maximum plasma concentration (C_max ), 0-12-hour area under the concentration-time curve (AUC_0-12 hour ), and trough plasma concentration (C_trough ) ranged from 0.92-fold to 1.15-fold, indicating good predictive performance. The model quantitatively indicated the impact of cytochrome P450 (CYP)3A4 abundance, hematoc

SUBMITTER: Emoto C 

PROVIDER: S-EPMC6539708 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature