Caution with PBPK modeling based on the In Vitro Kinetics for Bilirubin Hepatic Uptake and Glucuronidation: commentary on Dong et al.

John O. Miners; Thomas M. Polasek

doi:10.1002/cpt.3734

Caution with PBPK modeling based on the In Vitro Kinetics for Bilirubin Hepatic Uptake and Glucuronidation: commentary on Dong et al.

John O. Miners, Thomas M. Polasek

College of Medicine and Public Health

Research output: Contribution to journal › Comment/debate

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Abstract

PBPK modeling is increasingly used to predict clearance and
pharmacokinetic interactions, and to understand their molecular
mechanisms. The hepatic uptake (OATP1B1 and OATP1B3)
and glucuronidation (UGT1A1) of bilirubin can be inhibited
by various drugs, resulting in hyperbilirubinemia. Predicting
the relative contributions of these molecular pathways to the
pharmacokinetics of bilirubin and its interactions is made difficult
by the highly variable in vitro kinetic parameters available for
PBPK modeling.

Original language	English
Number of pages	3
Journal	Clinical Pharmacology and Therapeutics
DOIs	https://doi.org/10.1002/cpt.3734
Publication status	E-pub ahead of print - 26 May 2025

Keywords

In Vitro Kinetics
Bilirubin Hepatic
Glucuronidation
pharmacokinetic

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Final published verisonFinal published version, 97.2 KBLicence: CC BY-NC-ND

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title = "Caution with PBPK modeling based on the In Vitro Kinetics for Bilirubin Hepatic Uptake and Glucuronidation: commentary on Dong et al.",

abstract = "PBPK modeling is increasingly used to predict clearance andpharmacokinetic interactions, and to understand their molecularmechanisms. The hepatic uptake (OATP1B1 and OATP1B3)and glucuronidation (UGT1A1) of bilirubin can be inhibitedby various drugs, resulting in hyperbilirubinemia. Predictingthe relative contributions of these molecular pathways to thepharmacokinetics of bilirubin and its interactions is made difficultby the highly variable in vitro kinetic parameters available forPBPK modeling.",

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AU - Polasek, Thomas M.

PY - 2025/5/26

Y1 - 2025/5/26

N2 - PBPK modeling is increasingly used to predict clearance andpharmacokinetic interactions, and to understand their molecularmechanisms. The hepatic uptake (OATP1B1 and OATP1B3)and glucuronidation (UGT1A1) of bilirubin can be inhibitedby various drugs, resulting in hyperbilirubinemia. Predictingthe relative contributions of these molecular pathways to thepharmacokinetics of bilirubin and its interactions is made difficultby the highly variable in vitro kinetic parameters available forPBPK modeling.

AB - PBPK modeling is increasingly used to predict clearance andpharmacokinetic interactions, and to understand their molecularmechanisms. The hepatic uptake (OATP1B1 and OATP1B3)and glucuronidation (UGT1A1) of bilirubin can be inhibitedby various drugs, resulting in hyperbilirubinemia. Predictingthe relative contributions of these molecular pathways to thepharmacokinetics of bilirubin and its interactions is made difficultby the highly variable in vitro kinetic parameters available forPBPK modeling.

KW - In Vitro Kinetics

KW - Bilirubin Hepatic

KW - Glucuronidation

KW - pharmacokinetic

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JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

ER -

Caution with PBPK modeling based on the In Vitro Kinetics for Bilirubin Hepatic Uptake and Glucuronidation: commentary on Dong et al.

Abstract

Keywords

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