Description
Trimethoprim inhibits OCT2-mediated renal secretion of metformin, increasing metformin plasma concentrations and potentially raising the risk of lactic acidosis in susceptible patients.
Mécanisme
Trimethoprim is a competitive inhibitor of OCT2 and MATE1/2 transporters in renal proximal tubules, which are responsible for active secretion of metformin; inhibition significantly reduces metformin clearance.
Signification clinique
Pharmacokinetic studies show trimethoprim increases metformin AUC by approximately 27%; in patients with renal impairment this effect is amplified and lactic acidosis risk increases.
Prise en charge
Use with caution in patients with renal impairment; consider reducing metformin dose or temporarily withholding it during trimethoprim courses in high-risk patients; monitor renal function.