Physiologically-Based Pharmacokinetic Modeling of the Drug–Drug Interaction of the UGT Substrate Ertugliflozin Following Co-Administration with the UGT Inhibitor Mefenamic Acid

14Citations
Citations of this article
26Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The sodium-glucose cotransporter 2 inhibitor ertugliflozin is metabolized by the uridine 5'-diphospho-glucuronosyltransferase (UGT) isozymes UGT1A9 and UGT2B4/2B7. This analysis evaluated the drug–drug interaction (DDI) following co-administration of ertugliflozin with the UGT inhibitor mefenamic acid (MFA) using physiologically-based pharmacokinetic (PBPK) modeling. The ertugliflozin modeling assumptions and parameters were verified using clinical data from single-dose and multiple-dose studies of ertugliflozin in healthy volunteers, and the PBPK fraction metabolized assignments were consistent with human absorption, distribution, metabolism, and excretion results. The model for MFA was developed using clinical data, and in vivo UGT inhibitory constant values were estimated using the results from a clinical DDI study with MFA and dapagliflozin, a UGT1A9 and UGT2B4/2B7 substrate in the same chemical class as ertugliflozin. Using the verified compound files, PBPK modeling predicted an ertugliflozin ratio of area under the plasma concentration–time curves (AUCR) of 1.51 when co-administered with MFA. ClinicalTrials.gov identifier: NCT00989079.

Cite

CITATION STYLE

APA

Callegari, E., Lin, J., Tse, S., Goosen, T. C., & Sahasrabudhe, V. (2021). Physiologically-Based Pharmacokinetic Modeling of the Drug–Drug Interaction of the UGT Substrate Ertugliflozin Following Co-Administration with the UGT Inhibitor Mefenamic Acid. CPT: Pharmacometrics and Systems Pharmacology, 10(2), 127–136. https://doi.org/10.1002/psp4.12581

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free