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

Abstract

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. 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 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. 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.