Anastrozole
Anastrozole. Triazole-based reversible competitive aromatase (CYP19) inhibitor. Blocks peripheral conversion of androgens (testosterone… Oral half-life 2.1 d.
Triazole-based reversible competitive aromatase (CYP19) inhibitor. Blocks peripheral conversion of androgens (testosterone, androstenedione) to estrogens (estradiol, estrone) — the dominant estrogen source in postmenopausal women. >96% aromatase inhibition + >80% estradiol suppression at 1 mg/d. No effect on adrenal steroidogenesis at therapeutic doses (distinguishes from older steroidal AIs like aminoglutethimide). Also used off-label in men on TRT or AAS to control aromatisation-driven gynaecomastia.
PK: THE HALF-LIFE WAS RIGHT UNDER A CITATION THAT GIVES ONLY A RANGE. The old source says "The elimination half-life of ARIMIDEX in humans ranged from 30 to 60 h", and 50 is not even its midpoint; the replacement states it verbatim, "The drug terminal half-life after multiple doses is 50 hours". F 0.85 and V 140 L ARE UNSOURCEABLE - a PubMed search for an anastrozole volume of distribution returns COUNT 0, twice - AND THEY ARE KEPT ANYWAY, because they reproduce the only human exposure measurement in the literature almost exactly: {140, 0.85, 50} imply CL/F 2.283 L/h against an observed "AUC(0-infinity) ... (443 +/- 141) ... microg . h . L-1" at 1 mg, which is 2.257 L/h. A 1.2% match. That is almost certainly a class-9 back-derivation from this very AUC, but it is a CORRECT one, and deleting it would make the model worse; it is annotated as model-derived rather than measured. TWO TRAPS AVOIDED AND RECORDED: the same exposure paper "relative bioavailability ... 100 % +/- 9 %" is RELATIVE and unusable for F, and a microdose cassette study F figures of 34.9% and 18.4% belong to CETROZOLE and TMD-322, not to anastrozole. PK: ABSORPTION RATE AUTHORED FROM THE ARIMIDEX LABEL. This row carried no ka, so the solver substituted 1.0/h and put the peak at 4.3 h. Source, verbatim from the current FDA label (DailyMed setid acbfaaa9-503c-4691-9828-76a7146ed6de): "The mean C max of anastrozole decreased by 16% and the median T max was delayed from 2 to 5 hours when anastrozole was administered 30 minutes after food" — so the FASTED median, which is the state this record models, is 2 hours. PUBMED HAS THIS NOWHERE — 27 targeted searches across two passes returned four usable peak times for this whole class, because Tmax is a label figure that rarely reaches an abstract. A regulatory label is already a first-class source in this schema. With the stored half-life fixing ke, Tmax solves uniquely for ka by inverting the model own definition, ln(ka/ke)/(ka-ke) = Tmax — ARITHMETIC, NOT AN ESTIMATE — giving 2.638/h, which reproduces 2 h on substitution. EXPOSURE IS UNCHANGED: the absorption rate cancels out of AUC, so only the shape moves.
Pharmacokinetics
- Oral — t½ 2.1 d · F 85% · ka 2.638 h⁻¹ · Vd 140 L
Related compounds
- Tamoxifen — caution
- Testosterone (TRT) — synergistic
- Letrozole — warn
Sources: PMID:7626450, PMID:8903429, PMID:9522927, PMID:11747767