Identification of Transporter Polymorphisms Influencing Metformin Pharmacokinetics in Healthy Volunteers.

For patients with type 2 diabetes, metformin is the most often recommended drug. However, there are substantial individual differences in the pharmacological response to metformin. To investigate the effect of transporter polymorphisms on metformin pharmacokinetics in an environment free of confounding variables, we conducted our study on healthy participants. This is the first investigation to consider demographic characteristics alongside all transporters involved in metformin distribution. Pharmacokinetic parameters of metformin were found to be affected by age, sex, ethnicity, and several polymorphisms. Age and and polymorphisms affected the area under the concentration-time curve (AUC). However, after adjusting for dose-to-weight ratio (dW), sex, age, and ethnicity, along with and , influenced AUC. The maximum concentration was affected by age and , but after adjusting for dW, it was affected by sex, age, ethnicity, , and . The time to reach the maximum concentration was influenced by sex, like half-life, which was also affected by . The volume of distribution and clearance was affected by sex, age, ethnicity and . Alternatively, the pharmacokinetics of metformin was unaffected by polymorphisms in , , , or . Therefore, our study demonstrates that a multifactorial approach to all patient characteristics is necessary for better individualization.