Methimazole
Methimazole. Thionamide antithyroid — inhibits thyroid peroxidase (TPO) blocking iodination of thyroglobulin tyrosines → halts thyroid hormone… Oral half-life 5 h.
Thionamide antithyroid — inhibits thyroid peroxidase (TPO) blocking iodination of thyroglobulin tyrosines → halts thyroid hormone synthesis. First-line for Graves disease + thyroid storm (after PTU in early pregnancy). Agranulocytosis is the feared adverse effect.
PK: MY CARBIMAZOLE CONCERN IS REFUTED AND A 2x ARITHMETIC MISS IS DELIBERATELY ACQUITTED. The analyte question is settled by the citation itself, which dosed methimazole directly by both routes — "Following intravenous administration of 10mg to healthy subjects" and "absolute bioavailability after oral administration of 10mg methimazole in the fasting state was high, with a mean of 93%" — so these are not carbimazole-derived values. The clearance test fires at 2.0x against a review stating "a total clearance of about 200ml/minute", AND THAT REVIEW CONTRADICTS ITSELF: its own 40 L volume and 200 mL/min imply a 2.3 h half-life against its own stated 3 to 5 hours. The likely explanation is in the same literature — "Incomplete absorption of carbimazole could explain particular high apparent volumes of distribution and apparent clearances" — so that figure is plausibly an inflated apparent clearance from carbimazole dosing. A 40 L volume is about total body water, which is right for a 114-dalton virtually unbound drug, and pairing it with the primary intravenous half-life is the more defensible set. RECORDED AS A NEAR-MISS SO NOBODY "CORRECTS" IT. The volume is verbatim but in a DIFFERENT reference than the one cited for it, and both are already present. THE EMPTY EFFECT COMPARTMENT IS ALSO CORRECT: this drug is "concentrated in the thyroid gland, exerting an effect on intrathyroidal iodine metabolism for periods exceeding those in which serum concentrations can be measured", which a keo cannot represent. PK: THE STORED ABSORPTION RATE WAS THE SOLVER DEFAULT WEARING A CITATION. A ka of 1.0/h is exactly what resolvePk substitutes when the field is ABSENT, and no source on this record states one. Removing it is NUMERICALLY A NO-OP — the resolver supplies the identical number — so no curve moves; what changes is that the record stops asserting an absorption rate it never measured. This is the same shape already found on a volume of 35 L, which is likewise the default at the seventy-kilogram reference. THE WIDER DEBT IS LEFT ALONE ON PURPOSE: twelve values account for 152 of the 276 authored absorption rates, but the other eleven are NOT the default, so deleting those would move their curves rather than leave them, which is the error this audit spent a batch documenting.
Pharmacokinetics
- Oral — t½ 5 h · F 93% · Vd 40 L
Sources: PMID:4042519, PMID:6172233