Repaglinide (caution): CYP2C8 inhibition. Niemi 2004 (PMID:15025742) verbatim: "Trimethoprim raised the AUC(0, infinity) and C(max) of repaglinide by 61% (range, 30-117%; P= 0.0008)". 9 healthy volunteers, randomized double-blind crossover, trimethoprim 160 mg bid × 3d + single 0.25 mg PO repaglinide. AUC ratio 1.61×; Ki ≈ 3/0.61 = 4.92 µM. Diabetic patients on TMP-SMX for UTI face hypoglycemia risk.
Rosiglitazone (caution): CYP2C8 inhibition. Niemi 2004 (PMID:15371985) verbatim: "trimethoprim raised the area under the plasma rosiglitazone concentration-time curve [AUC(0-infinity)] by 37% (range, 16% to 51%; P <.0001)". 10 healthy volunteers, randomized crossover, trimethoprim 160 mg bid × 4d + single 4 mg PO rosiglitazone. AUC ratio 1.37×; Ki ≈ 3/0.37 = 8.11 µM. Sub-2× but reproducible; relevant at higher TZD doses.
Pioglitazone (caution): CYP2C8 inhibition. Tornio 2008 (PMID:17913794) verbatim: "Trimethoprim raised the area under the plasma pioglitazone concentration-time curve (AUC(0-infinity)) by 42% (p < 0.001)". 16 healthy volunteers stratified by CYP2C8 genotype, randomized crossover, trimethoprim 160 mg bid × 6d + 15 mg PO pioglitazone d3. AUC ratio 1.42×; Ki ≈ 3/0.42 = 7.14 µM.