Cited 0 times in

Effect of Rifampicin on the Pharmacokinetics of Evogliptin in Healthy Volunteers

 Yesong Shin  ;  Chungam Choi  ;  Eun Sil Oh  ;  Choon Ok Kim  ;  Kyungsoo Park  ;  Min Soo Park 
 DRUG DESIGN DEVELOPMENT AND THERAPY, Vol.16 : 4301-4310, 2022-12 
Journal Title
Issue Date
Antiviral Agents ; Area Under Curve ; Cross-Over Studies ; Cytochrome P-450 CYP3A / metabolism ; Diabetes Mellitus, Type 2* ; Dipeptidyl-Peptidase IV Inhibitors* / pharmacology ; Drug Interactions ; Healthy Volunteers ; Humans ; Hypoglycemic Agents ; Piperazines / pharmacokinetics ; Protease Inhibitors ; Rifampin / pharmacology
CYP3A inducer ; DPP-4 inhibitor ; drug–drug interaction ; evogliptin ; rifampicin
Purpose: Evogliptin (DA-1229) is a novel, potent, and selective dipeptidyl peptidase 4 (DPP-4) inhibitor for treating type 2 diabetes mellitus. This study investigates the effect of rifampicin on evogliptin pharmacokinetics.

Patients and methods: An open-label, crossover, one-sequence study was conducted on 12 healthy subjects. Reference baseline pharmacokinetic samples were collected on day 1 after the subjects were administered a single dose of 5 mg evogliptin. After a washout period, the subjects were administered 600 mg rifampicin once daily for 10 days, from days 8 to 17, for full induction of hepatic enzyme activity. On day 17, single doses of evogliptin (5 mg) were administered along with rifampicin (600 mg). The test pharmacokinetic samples were collected with a sampling schedule identical to that used for the reference.

Results: Maximum concentration (Cmax) and area under the plasma drug concentration-time curve (AUC0-96h) of evogliptin with and without co-administration of rifampicin were compared. Reference and test Cmax and AUC0-96h values of evogliptin were 4.70 ng/mL vs 4.86 ng/mL and 153.97 ng∙h/mL vs 58.83 ng∙h/mL, respectively. All adverse events were mild in intensity and considered unrelated to evogliptin administration.

Conclusion: Rifampicin decreased the AUC0-96h of evogliptin by 61.8% without significantly affecting Cmax. The mechanism underlying the decrease in AUC0-96h is thought to be the induction of cytochrome P450 (CYP), especially 3A, by rifampicin. The adverse events, none of which were serious, were not significantly altered by the concomitant administration of evogliptin and rifampicin. Nevertheless, it would be prudent that evogliptin dosing should be carefully considered when co-administered with CYP3A inducers.
Files in This Item:
T9992022817.pdf Download
Appears in Collections:
6. Others (기타) > Dept. of Clinical Pharmacology (임상시험센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Choon Ok(김춘옥) ORCID logo
Park, Kyungsoo(박경수) ORCID logo
Park, Min Soo(박민수) ORCID logo
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.