Levothyroxine
Levothyroxine, a hormone. Synthetic L-isomer of thyroxine (T4). Peripherally deiodinated by DIO1/2 to active T3 — provides physiologic hormone… Oral half-life 7.2 d.
Synthetic L-isomer of thyroxine (T4). Peripherally deiodinated by DIO1/2 to active T3 — provides physiologic hormone with controlled release. Narrow therapeutic index; TSH-guided titration every 6–8 weeks. Absorption disrupted by many things — take fasting separate from calcium/iron/PPIs/antacids.
VOLUME AND HALF-LIFE REBUILT 2026-09-27, both routes. The previous V 11 L and t1/2 168 h were hung on PMID:6688797, whose whole abstract is 689 characters and states neither. That paper collected serum data over a period of 50 h — SHORTER THAN THE 168 h HALF-LIFE THE RECORD CLAIMED, which it therefore could not have measured. 11 L was also 0.157 L/kg at the reference weight, one of the shared per-kilogram priors pk.template-volume now reports. The replacements come from a stable-isotope 13C-LT4 study. PMID:29212434 states verbatim that CL/F, V/F and Tmax "were estimated to be 0.712 L/h, 164.9 L, 4 h". PMID:29212434 reports the "half-life of the terminal distribution phase" verbatim as "and 172.2 h, respectively", and the half-life is stored at that 172.2 h. THE VOLUME IS A DECLARED DERIVATION, because 164.9 L is an APPARENT V/F and FIELDS forbids pairing an apparent volume with an independent F: the resolver already multiplies by F, so storing 164.9 beside F 0.66 would correct for bioavailability twice. Arithmetic: V = (V/F) x F = 164.9 x 0.66 = 108.8 L. The F input is the 0.66 quoted on the PO row, so THE TWO INPUTS ARE DIFFERENT STUDIES (a 2018 isotope study and a 1983 tablet study) and that is the derivation’s weakest joint; it is declared rather than hidden. An absolute volume is a property of the molecule, so the same 108.8 L is stored on the IV route. COHERENCE CHECK: 108.8 L with t1/2 172.2 h implies CL = ln2/172.2 x 108.8 = 0.438 L/h, against 0.712 x 0.66 = 0.47 L/h from the same paper’s CL/F. Seven percent apart, which is the slack that paper carries internally (its stated 172.2 h against the 160.5 h its own V/F and CL/F imply), so the stored numbers are jointly possible.
Pharmacokinetics
- Oral — t½ 7.2 d · F 66% · ka 1.481 h⁻¹ · Vd 108.8 L
- IV — t½ 7.2 d · F 100% · Vd 108.8 L
Related compounds
- Calcium — caution
- Iron — caution
- Liothyronine (T3) — synergistic
- Cholestyramine — caution
Sources: PMID:30349610, PMID:29212434