Back to Search Start Over

Pharmacokinetic Interaction between Metformin and Verapamil in Rats: Inhibition of the OCT2-Mediated Renal Excretion of Metformin by Verapamil

Authors :
Seung Yon Han
Young Hee Choi
Source :
Pharmaceutics, Vol 12, Iss 5, p 468 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

The incidence of hypertension in diabetic patients has been increasing and contributing to the high mortality of diabetic patients. Recently, verapamil use was found to lower fasting blood glucose levels in diabetic patients, which led to a new indication of verapamil as combination treatment with anti-diabetic agents such as metformin. As pharmacokinetic (PK) interaction can affect drug efficacy and safety in drug combination, their PK-based interaction is recommended to be evaluated in preclinical levels as well as clinical levels. In case of metformin and verapamil, organic cation transporter (OCT) 1 and 2 primarily mediate metformin distribution to the liver and its elimination into urine, whereas cytochrome P450 is responsible for the hepatic metabolism of verapamil. Verapamil is also known as a potential OCT2 inhibitor. Thus, PK interaction between metformin (30 mg/kg) and verapamil (20 mg/kg) were investigated after their simultaneous administration to rats. In our results, verapamil inhibited the OCT2-mediated renal excretion of metformin, subsequently leading to increase of the systemic exposure of metformin. In contrast, metformin did not influence the pharmacokinetic pattern of verapamil. Although the further clinical investigation is required, our finding suggests a possibility of OCT2-mediated interaction of metformin and verapamil.

Details

Language :
English
ISSN :
19994923
Volume :
12
Issue :
5
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.9ab3fb1791e34bbcb12566005123bf99
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics12050468