Effect of Rifampicin on the Pharmacokinetics of Evogliptin in Healthy Volunteers

• Published in: Drug design, development and therapy development and therapy, 2022-01, Vol.16, p.4301-4310
• Main Authors: Shin, Yesong, Choi, Chungam, Oh, Eun Sil, Kim, Choon Ok, Park, Kyungsoo, Park, Min Soo
• Format: Article
• Language: English
• Subjects: Adverse events; Antiviral Agents; Area Under Curve; Caffeine; Cross-Over Studies; cyp3a inducer; Cytochrome; Cytochrome P-450; Cytochrome P-450 CYP3A - metabolism; Cytochrome P450; Cytochromes P450; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors - pharmacology; Dosage; Dosage and administration; dpp-4 inhibitor; Drug dosages; Drug Interactions; drug–drug interaction; Enzymatic activity; Enzyme activity; Enzymes; evogliptin; Healthy Volunteers; Humans; Hypoglycemic Agents; Metabolites; Original Research; Peptidase; Pharmacokinetics; Pharmacology; Piperazines - pharmacokinetics; Plasma; Protease Inhibitors; rifampicin; Rifampin; Rifampin - pharmacology; Type 2 diabetes
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S383157

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. 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. Maximum concentration (C ) and area under the plasma drug concentration-time curve (AUC ) of evogliptin with and without co-administration of rifampicin were compared. Reference and test C and AUC 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. Rifampicin decreased the AUC of evogliptin by 61.8% without significantly affecting C . The mechanism underlying the decrease in AUC 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.