Trimetazidine
Trimetazidine. Partial fatty-acid-oxidation inhibitor — selectively inhibits long-chain 3-ketoacyl-CoA thiolase (LC-KAT), the terminal enzyme of… Oral half-life 4.7 h.
Partial fatty-acid-oxidation inhibitor — selectively inhibits long-chain 3-ketoacyl-CoA thiolase (LC-KAT), the terminal enzyme of mitochondrial β-oxidation. Shifts myocardial ATP production from free-fatty-acid oxidation toward glucose oxidation, which requires ~10–13% less oxygen per ATP generated — protects ischaemic myocardium without hemodynamic effects (no change in heart rate, BP, or contractility). Second-line add-on for stable angina. Also used off-label in heart failure, tinnitus, and vertigo. Listed on the WADA prohibited list since 2014 (category S4 — hormone and metabolic modulators).
PK: THE CITED PAPER STUDIED A DIFFERENT PRODUCT, AND THE Cmax-OVER-AUC IDENTITY PROVED ITS NUMBERS UNUSABLE. It is a bioequivalence study of two 35 mg MODIFIED-RELEASE formulations while this record doses the 20 mg immediate-release tablet, and BOTH OF ITS ARMS FALL BELOW THE ONE-COMPARTMENT FLOOR — exposure over peak of 4.695 and 4.510 hours against floors of 4.977 and 5.324 — so NO CHOICE OF ABSORPTION RATE, VOLUME OR BIOAVAILABILITY COULD HAVE FITTED THEM. The physical reason is benign, because it is a modified-release product and this solver does have a zero-order input term, but the right repair for a 20 mg immediate-release record is a different citation. The replacement dosed exactly this product at exactly this dose, and ITS QUARTET PASSES THE IDENTITY ALMOST EXACTLY, at 0.982 and 1.007 across two arms. The stored bioavailability was never absolute — that study reports only ratios of 106.19%, 104.74% and 106.30% — and the stored volume was back-derived from its exposure and half-life. The old set also asserted a clearance of 1250 mL/min FOR A DRUG SIXTY PERCENT RENALLY EXCRETED UNCHANGED, several-fold above filtration and above hepatic blood flow; it faithfully encoded a number that is itself an outlier. A NEAR-MISS: the stored ka of 1.0 IS THE SOLVER OWN DEFAULT AND IS ESSENTIALLY RIGHT, within 3% of the properly-sourced value.
Pharmacokinetics
- Oral — t½ 4.7 h · F 100% · ka 1.028 h⁻¹ · Vd 197.6 L
Sources: PMID:10439934, PMID:17208404, PMID:21899207