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Licensed Unlicensed Requires Authentication Published by De Gruyter September 1, 2017

Effects of the genetic variants of organic cation transporters 1 and 3 on the pharmacokinetics of metformin in Jordanians

Nancy Hakooz, Yazun Bashir Jarrar, Malik Zihlif, Amer Imraish, Saja Hamed and Tawfiq Arafat

Abstract

Background:

Human response to the antidiabetic metformin is influenced by some factors, such as genetic variants in the SLC22A genes. This study aimed to determine the frequency of main SLC22A1 and SLC22A3 genetic variants and their influence on metformin pharmacokinetics among healthy unrelated Arab Jordanians.

Patients and methods:

The SLC22A1 and SLC22A3 genes were genotyped by DNA sequencing of exons 1, 3, 7, and 9 in the SLC22A1 gene and exons 6, 7, and 9 in the SLC22A3 gene. Then, a clinical pharmacokinetic study was conducted on 26 healthy volunteers. The pharmacokinetic parameters were calculated using non-compartmental model analysis. The study was an open-label, randomized study with single 1000 mg metformin administration.

Results:

Results showed that volunteers with SLC22A3 rs8187722 variant had higher (χ2, p<0.05) metformin Cmax and AUC values than the wild SLC22A3 volunteers, whereas T½ and Kel were not affected. In addition, volunteers with the heterozygote SLC22A3 rs2292334 variant had significantly higher (χ2, p<0.05) metformin Cmax and AUC and lower Kel values than the wild-type SLC22A3 genotype.

Conclusions:

The SLC22A3 rs8187722 and rs2292334 genetic variants affected metformin pharmacokinetics among a clinical sample of Jordanians. The findings may increase our understanding of the inter-individual and inter-ethnic variations in metformin response.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by a grant of the Deanship of Academic Research at The University of Jordan.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2017-5-31
Accepted: 2017-8-9
Published Online: 2017-9-1
Published in Print: 2017-9-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

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