Trimethoprim
Trimethoprim. Antifolate — inhibits bacterial dihydrofolate reductase (DHFR), blocking tetrahydrofolate synthesis downstream of… Oral half-life 11 h.
Antifolate — inhibits bacterial dihydrofolate reductase (DHFR), blocking tetrahydrofolate synthesis downstream of sulfamethoxazole's DHPS step. Synergistic when combined. Modest renal tubular K+ secretion blockade → hyperkalemia.
PK re-sourced to Chin 1995 (PMID:7695325), adult patients dosed intravenously and then switched to oral in the SAME subjects, with trimethoprim reported separately from sulfamethoxazole — verbatim "volume of distribution, 1.6 +/- 0.5 versus 1.5 +/- 0.5 liters/kg", "half-life, 10.9 +/- 7.4 versus 11.3 +/- 4.0 h" and "bioavailability was 97.5% +/- 22.4% versus 101.8% +/- 22.7% for trimethoprim". Volumes are the per-kilogram figures scaled to 70 kg, and F is pinned to 1 since the measurement is effectively complete. The previous citation studied FOUR CHILDREN WITH BILIARY ATRESIA, reported a half-life whose standard deviation exceeded its mean, and contained no intravenous arm at all though the IV row cited it. INTERACTIONS: ALL THREE AFFINITIES ARE THE SAME ALGEBRA — the verbatim exposure rise inverted through one assumed concentration of 3.0 µM, which is within twenty percent of this record own modelled mean plasma level. The block reconstructs exactly on every edge, which is what makes it safe to relabel rather than remove.
Pharmacokinetics
- Oral — t½ 11.3 h · F 100% · Vd 105 L
- IV — t½ 10.9 h · F 100% · Vd 112 L
Related compounds
- Repaglinide — caution
- Rosiglitazone — caution
- Pioglitazone — caution
Sources: PMID:8696062, PMID:15025742, PMID:15371985, PMID:17913794, PMID:7695325