Evaluation of the Pharmacokinetics of Metformin Following Coadministration With Doravirine in Healthy Volunteers.

Doravirine is a novel nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus type-1 (HIV-1) infection. In vitro and clinical data suggest that doravirine is unlikely to cause significant drug-drug interactions via major drug-metabolizing enzymes or transporters. As a common HIV-1 infection comorbidity, type 2 diabetes mellitus is often treated with metformin. Perturbations of metformin absorption or elimination may affect its safety and efficacy profile; therefore, understanding potential drug-drug interactions between doravirine and metformin is important. An open-label, fixed-sequence, 2-period trial in healthy adults was conducted. Single-dose metformin 1000 mg was administered in period 1; in period 2, doravirine 100 mg was administered once daily on days 1 to 7, and single-dose metformin 1000 mg was administered on day 5. Plasma pharmacokinetics for metformin alone and coadministered with doravirine were assessed. Fourteen participants enrolled and completed the trial. Least-squares geometric mean ratios and 90% confidence intervals of metformin AUC0-∞ , and Cmax following coadministration of metformin and doravirine compared with metformin alone were 0.94 (0.88-1.00) and 0.94 (0.86-1.03), respectively; metformin Tmax and half-life were also minimally impacted. These data indicate that doravirine did not have a clinically relevant effect on the pharmacokinetics of metformin. Metformin alone and coadministered with doravirine was generally well tolerated. These data support coadministration of doravirine 100 mg and metformin 1000 mg without dose adjustment.