A phase I, open-label, 2-part study to establish absolute bioavailability and the absorption, metabolism and excretion of evogliptin in healthy male subjects by a light-label approach

Song, Ji Su; Lee, Dong Hoon; Shim, Hongjin; Lee, Hee Joo; La, Sookie; Deuker, Stephen R.; Walker, Helen; Collier, Jo; Shaw, Iain

doi:10.1016/j.dmpk.2016.10.307

Cited by 3 publications

(2 citation statements)

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“…4,5 The absolute bioavailability was reported to be about 50%. 6 In a clinical trial on type 2 diabetes, administration of 5 mg of evogliptin once daily for 12 weeks reduced glycated hemoglobin (HbA1c) by 0.66% compared with a decrease of 0.09% in the control group. 7 Patients with type 2 diabetes taking DPP-4 inhibitors commonly consume additional antidiabetic medications, such as metformin, sulfonylureas, or thiazolidinediones.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Rifampicin on the Pharmacokinetics of Evogliptin in Healthy Volunteers

Shin¹,

Choi²,

Oh³

et al. 2022

DDDT

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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 (C max ) and area under the plasma drug concentration-time curve (AUC 0-96h ) of evogliptin with and without co-administration of rifampicin were compared. Reference and test C max and AUC 0-96h 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 AUC 0-96h of evogliptin by 61.8% without significantly affecting C max . The mechanism underlying the decrease in AUC 0-96h 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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Rifampicin on the Pharmacokinetics of Evogliptin in Healthy Volunteers

Shin¹,

Choi²,

Oh³

et al. 2022

DDDT

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Population pharmacokinetic and pharmacodynamic model of evogliptin: Severe uremia increases the bioavailability of evogliptin

Kim,

Lee

et al. 2024

CPT Pharmacom & Syst Pharma

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Uremia, a condition characterized by the retention of uremic toxins due to impaired renal function, may affect drug metabolism mediated by CYP3A4 enzymes. Evogliptin is a dipeptidyl peptidase‐4 (DPP‐4) inhibitor diabetic drug that is primarily metabolized by CYP3A4. This study aimed to construct a population pharmacokinetic (PK) and pharmacodynamic (PD) model for evogliptin in patients with varying degrees of renal disease, including end‐stage renal disease on hemodialysis. A total of 688 evogliptin concentration and 598 DPP‐4 activity data were available from 46 subjects. PK and PD data analyses were performed using a nonlinear mixed‐effects model. The PK of evogliptin was optimally described by a two‐compartment model with first‐order absorption. The significant covariates in the final model included blood amylase and triglyceride on F1 (relative bioavailability). The simulation findings, together with previously reported PK data, provided evidence of a significant inhibition of the first‐pass effect of evogliptin in patients with renal impairment. A direct link sigmoidal Emax model was developed to describe the relationship between evogliptin concentration and DPP‐4 inhibition. The PD model predicted significant inhibition of DPP‐4 at maximum effect (Emax: 88.9%) and a low EC50 value (1.08 μg/L), indicating the high potency and efficacy of evogliptin. The developed PK/PD model accurately predicted exposure and the resulting DPP‐4 activity of evogliptin in renal impairment. The findings of this study suggest that renal impairment and associated biochemical changes may impact the bioavailability of CYP3A4‐metabolized drugs.

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Possibility of pharmacokinetic drug interaction between a DPP-4 inhibitor and a SGLT2 inhibitor

Park

Chung

et al. 2020

Transl Clin Pharmacol

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A phase I, open-label, 2-part study to establish absolute bioavailability and the absorption, metabolism and excretion of evogliptin in healthy male subjects by a light-label approach

Cited by 3 publications

References 0 publications

Effect of Rifampicin on the Pharmacokinetics of Evogliptin in Healthy Volunteers

Effect of Rifampicin on the Pharmacokinetics of Evogliptin in Healthy Volunteers

Population pharmacokinetic and pharmacodynamic model of evogliptin: Severe uremia increases the bioavailability of evogliptin

Possibility of pharmacokinetic drug interaction between a DPP-4 inhibitor and a SGLT2 inhibitor

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