Effect of Rifampin on the Pharmacokinetics of Ertugliflozin in Healthy Subjects

Clinical Therapeutics
Vikas K DawraDavid L Cutler

Abstract

Ertugliflozin is a selective sodium glucose cotransporter 2 inhibitor being developed for the treatment of type 2 diabetes mellitus. The primary enzyme involved in the metabolism of ertugliflozin is uridine diphosphate-glucuronosyltransferase (UGT) 1A9, with minor contributions from UGT2B7 and cytochrome P450 (CYP) isoenzymes 3A4, 3A5, and 2C8. Rifampin induces UGT1A9, UGT2B7, CYP3A4, and CYP3A5. Because concurrent induction of these enzymes could affect ertugliflozin exposure, this study assessed the effect of multiple doses of rifampin on the pharmacokinetic properties of single-dose ertugliflozin. Twelve healthy adult subjects were enrolled in this open-label, 2-period, fixed-sequence study and received ertugliflozin 15mg on day 1 of period 1, followed by rifampin 600mg once daily on days 1 to 10 in period 2. On day 8 of period 2, ertugliflozin 15mg was coadministered with rifampin 600mg. Plasma samples for ertugliflozin pharmacokinetic analysis were collected during 72hours after dosing on day 1 of period 1 and day 8 of period 2 and analyzed using a validated HPLC-MS/MS method. Pharmacokinetic parameters were calculated using noncompartmental analysis of concentration-time data. Natural log transformed AUC0-∞ and Cmax of er...Continue Reading

Citations

Apr 28, 2020·Clinical Pharmacokinetics·Daryl J FediukVaishali Sahasrabudhe
Jan 13, 2021·Clinical Pharmacology in Drug Development·Yinhua LiVaishali Sahasrabudhe
Nov 19, 2020·Clinical Pharmacology in Drug Development·Daryl J FediukKevin Sweeney
May 2, 2021·CPT: Pharmacometrics & Systems Pharmacology·Daryl J FediukVaishali Sahasrabudhe

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