Letrozole
Letrozole. Selectively and reversibly inhibits aromatase (CYP19A1), the rate-limiting enzyme converting testosterone to estradiol and… Oral half-life 42 h.
Selectively and reversibly inhibits aromatase (CYP19A1), the rate-limiting enzyme converting testosterone to estradiol and androstenedione to estrone. Reduces circulating estradiol by >95% in postmenopausal women. Does not affect cortisol or aldosterone synthesis at therapeutic doses.
PK: THE CLEANEST RECORD IN ITS GROUP — CORRECT TO 0.3% — AND NOT ONE VALUE CHANGES. Every number in it came from a paper that was never cited: "Letrozole absolute systemic bioavailability after p.o. administration was 99.9 +/- 16.3%. ... Total-body clearance of letrozole from plasma after i.v. administration was low (2.21 L h-1). The calculated distribution volume at steady state (1.87 L kg-1)". The stored bioavailability is that 99.9%, the stored volume is that 1.87 L/kg at the registry weight, and the stored half-life is what those two imply — 41.7 h. The record asserts a clearance of 2.2171 L/h against that paper verbatim INTRAVENOUS 2.21. CLASS 6 IS DEFINITIVELY ACQUITTED: this is a true steady-state volume from a study with a real intravenous arm, which is the acquittal shape the contract warns can be misread in either direction. The previously cited paper is a FOOD-EFFECT study containing none of the three values and stating only "in view of the half-life of about 2 d" — 48 h, not 42. A COINCIDENCE IS RECORDED SO IT IS NOT "DISCOVERED" LATER AS A DEFECT: the numeral 42 also appears in this literature as "half-life and AUC increased significantly by 42%", a textbook collision candidate — but the derivation from the same paper own volume and clearance is a far better explanation and makes the whole triple self-consistent. MY NON-LINEARITY PRIOR WAS REFUTED IN DIRECTION: clearance FALLS and half-life RISES at steady state, so the stored single-dose state under-predicts chronic exposure by about 28%.
Pharmacokinetics
- Oral — t½ 42 h · F 99% · Vd 133 L
Related compounds
- Anastrozole — warn
Sources: PMID:9267682, PMID:2149502, PMID:9725549, PMID:9429742, PMID:11745921