Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies

Tripathi, Alok Shiomurti; Timiri, Ajay Kumar; Mazumder, Papiya Mitra; Chandewar, A. V.

doi:10.1007/s00894-015-2823-x

Cited by 9 publications

(5 citation statements)

References 39 publications

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“…As warfarin is a probe drug of CYP2C9 and its pharmacokinetics is affected by CYP2C9 inhibitors and its genetic polymorphisms, we believe that even though glimepiride is metabolized by CYP2C9, it might not act as an inhibitor of CYP2C9. On the other hand, other studies revealed that glimepiride increased the plasma concentration of sildenafil, which is mainly metabolized by CYP3A4 . Therefore, it is possible to speculate that glimepiride is an inhibitor of CYP3A4.…”

Section: Discussionmentioning

confidence: 93%

Effect of glimepiride on the pharmacokinetics of teneligliptin in healthy Korean subjects

et al. 2019

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What is known and objective Teneligliptin is a DPP‐4 inhibitor used for the treatment of type 2 diabetes mellitus, commonly prescribed in combination with glimepiride. Teneligliptin is metabolized by CYP3A4, and glimepiride might be partly metabolized by CYP3A4. The aim of the study was to investigate the possible effect of glimepiride on the pharmacokinetics of teneligliptin in healthy subjects. Methods A repeated dose, open‐label, fixed‐sequence study was conducted in 26 healthy subjects. All participants were administered 20 mg teneligliptin daily for 6 days. On day 7, 4 mg glimepiride was administered together with 20 mg teneligliptin. Plasma teneligliptin concentrations were measured at a steady state, and its pharmacokinetic characteristics were compared without and with glimepiride. Results and discussion No statistically significant difference was found in the effect of glimepiride on teneligliptin pharmacokinetics. The steady‐state Cmax,ss values of teneligliptin without and with glimepiride were 207.01 ng/mL and 202.15 ng/mL, respectively. Its AUCτ values at steady‐state without and with glimepiride were 1527.8 ng · h/mL and 1578.6 ng · h/mL, respectively. The point estimation of geometric mean ratios (GMR) and the 90% confidence interval for both Cmax,ss and AUCτ were within the equivalence range of 0.8‐1.25. The results of the present study revealed that glimepiride did not cause pharmacokinetic interaction with teneligliptin in humans. What is new and conclusion Glimepiride did not affect the pharmacokinetic characteristics of teneligliptin in healthy subjects.

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Section: Discussionmentioning

confidence: 93%

Effect of glimepiride on the pharmacokinetics of teneligliptin in healthy Korean subjects

et al. 2019

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“…20,21 Evogliptin is mainly metabolized by CYP3A, whereas glimepiride might be a potential CYP3A4 inhibitor as evinced from the increased plasma concentration of sildenafil that is mainly metabolized by CYP3A4 in rats. 8,22 Additionally, evogliptin did not significantly change the PK properties of glimepiride that is mainly metabolized by CYP2C9, ie, evogliptin did not induce or inhibit CYP enzymes (unpublished in-house data). In addition, evogliptin and glimepiride did not affect the formation of each major metabolite.…”

Section: Discussionmentioning

confidence: 97%

<p>Pharmacokinetic/Pharmacodynamic Interactions Between Evogliptin and Glimepiride in Healthy Male Subjects</p>

Yoo¹,

Kim²,

Jang³

et al. 2020

DDDT

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Purpose: Evogliptin, a dipeptidyl peptidase-4 inhibitor, and glimepiride, a sulfonylurea, are used to treat type 2 diabetes mellitus. In this study, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between evogliptin and glimepiride. Materials and Methods: A randomized, open-label, 3-period, 3-treatment, 2-sequence crossover study was conducted in healthy male subjects. During each period, subjects received multiple doses of evogliptin 5 mg alone (EVO), glimepiride 4 mg alone (GLI), or a combination of the two (EVO+GLI). Serial blood and urine samples were collected 168 and 24 h post dosing, respectively, for PK and PD analyses. Results: Thirty-four subjects completed the study. The co-administration of evogliptin and glimepiride did not alter their plasma and urine PK profiles. For evogliptin, the geometric mean ratio (GMR) (90% confidence intervals) for the maximum plasma concentrations at steady-state (C max,ss) and the area under the curve during dosing interval at steady-state (AUC τ,ss) of EVO+GLI to E were 1.02 (0.98-1.06) and 0.97 (0.95-1.00), respectively. For glimepiride, the corresponding values of EVO+GLI to GLI were 1.08 (1.01-1.17) and 1.08 (1.02-1.14), respectively. All values were within the regulatory bioequivalence criteria of 0.8-1.25. Glucose excursion decreased with the co-administration of evogliptin and glimepiride compared with that observed with the evogliptin or glimepiride monotherapy. Conclusion: Evogliptin and glimepiride had no PK interactions when co-administered, while the combination therapy showed an additive glucose-lowering effect compared to those of evogliptin or glimepiride monotherapy.

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“…As previously mentioned, evogliptin is mainly metabolized by CYP3A, whereas glimepiride may be a CYP3A4 inhibitor, given that it increased the plasma concentration of sildenafil, mainly metabolized by CYP3A4 in rats. [5,16] , Additionally, it is believed that there is no significant change in PK properties of glimepiride, mainly metabolized by CYP2C9, as evogliptin does not induce nor inhibit CYP enzymes (unpublished inhouse data). This study actually revealed that the PK properties of glimepiride are not altered by evogliptin.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Interaction between Evogliptin and Glimepiride in Healthy Male Subjects

Yoo

Kim

Jang

et al. 2020

Preprint

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Aims: Evogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor and glimepiride, a sulfonylurea, have been used to treat type 2 diabetes mellitus. This study aimed at evaluating the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between evogliptin and glimepiride. Methods: A randomized, open-label, 3-period, 3-treatment, 2-sequence crossover study was conducted in healthy male subjects. During each period, subjects received multiple doses of evogliptin 5 mg alone (EVO), glimepiride 4 mg alone (GLI), or co-administration of the two (EVO+GLI). Serial blood and urine samples for PK and PD analyses were collected 168 and 24 hours post-dosing, respectively. Results: Thirty-four subjects completed the study. Coadministration of evogliptin and glimepiride did not alter their plasma and urine PK profiles. For evogliptin, the geometric mean ratio (GMR) (90% confidence intervals) for the maximum plasma concentrations at steady-state (Cmax,ss) and the area under the curve during dosing interval at steady-state (AUCτ,σς) of EVO+GLI to E were 1.02 (0.98 -1.06) and 0.97 (0.95 -1.00), respectively. For glimepiride, the corresponding values of EVO+GLI to GLI were 1.08 (1.01 -1.17) and 1.08 (1.02 -1.14), respectively. All values were within the regulatory bioequivalence criteria of 0.80 -1.25. Administration of EVO+GLI decreased the glucose excursion compared to evogliptin and glimepiride monotherapy, respectively. Conclusion: Evogliptin and glimepiride had no PK interactions when co-administered, while combination therapy showed an additive glucose lowering effect compared to those of evogliptin or glimepiride monotherapy.

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Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies

Cited by 9 publications

References 39 publications

Effect of glimepiride on the pharmacokinetics of teneligliptin in healthy Korean subjects

Effect of glimepiride on the pharmacokinetics of teneligliptin in healthy Korean subjects

<p>Pharmacokinetic/Pharmacodynamic Interactions Between Evogliptin and Glimepiride in Healthy Male Subjects</p>

Pharmacokinetic/Pharmacodynamic Interaction between Evogliptin and Glimepiride in Healthy Male Subjects

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