Tamoxifen
Tamoxifen. Triphenylethylene SERM. Tissue-selective ER agonism/antagonism: antagonist in breast (anti-proliferative, primary indication), partial… Oral half-life 4 d.
Triphenylethylene SERM. Tissue-selective ER agonism/antagonism: antagonist in breast (anti-proliferative, primary indication), partial agonist in bone (protective) + endometrium (hyperplasia / cancer risk) + liver (lipid + clotting-factor effects). Activity driven primarily by the CYP2D6-derived metabolite endoxifen (~100× ER affinity vs parent). In men: blocks hypothalamic ER-mediated negative feedback → raises LH/FSH → testicular testosterone — rationale for PCT after AAS cycles and off-label treatment of gynaecomastia.
PK: THE VOLUME AND THE HALF-LIFE CAME FROM DIFFERENT ERAS. The stored 96 h is verbatim and correctly the PARENT — "The half-lives of the drug and metabolite were approximately 4 and 9 days" — but the volume belongs with the modern 5-to-7-day figure, since the apparent volume implied by a measured steady-state exposure at a 6-day half-life is about 1367 L. Adam own abstract even flags the instability: "After three widely separated single doses, a reversible increase in elimination half-life occurred." Class 12 compounded by a superseded value. The repair keeps the VERBATIM half-life and moves the volume to reproduce the best exposure anchor, "the area under the plasma concentration versus time curve (AUC) of tamoxifen at steady state before [3.04 mg h/L; 90% CI, 2.71-3.44]" on 20 mg daily, against which the stored pair asserted a clearance 1.54x too high. F 1 IS A RELATIVE BIOAVAILABILITY READ AS ABSOLUTE — that paper compares a TABLET TO A SOLUTION, tamoxifen has no human intravenous form, and its absolute availability has never been measured — so F is pinned as a convention rather than a claim. ONE COMPARTMENT CANNOT SATISFY BOTH the steady-state exposure and this drug single-dose peak; exposure is preserved. MY WRONG-MASS PRIOR IS REFUTED BY ABSENCE: mw 371.51 IS the free base and this record has NO occupancy row for a mass error to propagate into. THE EFFECT COMPARTMENT IS REMOVED AND THE STANDING NO-ORPHAN RULE DOES NOT BLOCK IT, because this record carries no receptor_occupancy row for it to orphan. Its equilibration half-life was under fourteen hours against an antiestrogenic genomic response that builds over months, and it was seven times FASTER than this drug own elimination, so it was a null filter either way. ABSORPTION-RATE PROVENANCE: this value was derived by inverting the one-compartment peak-time relation in 2026-05-26-wave25-ka-from-tmax.ts, whose header claimed every peak time was verbatim from a primary human study. ALL FORTY-FOUR ENTRIES HAVE NOW BEEN CHECKED AND TWENTY-EIGHT FAIL. This one fails because the cited abstract reports exposure and peak fold-changes by genotype and no peak time — AND THIS IS ANOTHER OF THE FOUR ENTRIES NAMED AS SPOT-CHECK RE-CONFIRMED. It is DISCLOSED RATHER THAN DELETED: a midpoint of a narrow range is usually inside the true spread, and removing it would fall back on the solver default of 1.0 per hour, which is worse for most of these records.
Pharmacokinetics
- Oral — t½ 4.0 d · F 100% · ka 1.37 h⁻¹ · Vd 911 L
Related compounds
- Anastrozole — caution
- Paroxetine / strong CYP2D6 inhibitors — major
- Warfarin — major
- Clomiphene — caution
Sources: PMID:31008668, PMID:14618296, PMID:15911722, PMID:36836506, PMID:7427960, PMID:16361559