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Updated: Jan 28, 2026

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
A Theoretical Physiologically-Based Pharmacokinetic Approach to Ascertain Covariates Explaining the Large
Chie Emoto1,2, Trevor N Johnson3, David Hahn1
1Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
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 (Cmax ), 0-12-hour area under the concentration-time curve (AUC0-12 hour ), and trough plasma concentration (Ctrough ) 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, hematocrit, and serum albumin levels, in addition to CYP3A5 genotype status, on tacrolimus PK and associated variability. Age-dependent change in tacrolimus trough concentration in pediatric patients was mainly attributed to the CYP3A ontogeny profile. This study demonstrates the utility of PBPK modeling as a tool for mechanistic and quantitative assessment of the impact of patient physiological differences on observed large PK variability.
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