OCT2/MATE1 interactions

OCT2 carries organic cations from blood into the renal tubular cell and MATE1 pushes them on into urine — two steps of one secretory pathway.

Most substrates use both, and most inhibitors block both, so the pair is best learned as a single cohort. Inhibiting either step reduces net secretion and raises systemic exposure.

Metformin is the substrate that matters. Cimetidine, trimethoprim, dolutegravir, bictegravir, cobicistat, ranolazine, pyrimethamine, crizotinib and vandetanib all raise its exposure, which matters most when renal function is already marginal. Cisplatin, dofetilide and procainamide are the other substrates, and dofetilide has no margin to give.

Creatinine is itself an OCT2 and MATE1 substrate, and this is the single most useful thing on the page. Dolutegravir, bictegravir, cobicistat and trimethoprim block its secretion, so serum creatinine rises and estimated GFR appears to fall within days of starting them — with no actual change in filtration. The rise is early, small, stable and reversible, and a cystatin C-based estimate stays accurate. Recognizing it prevents an unnecessary workup and, worse, an unnecessary dose reduction.