Tirzepatide
Tirzepatide, a peptide. Synthetic 39-residue dual agonist at GLP-1R + GIP-R. Aib substitutions at positions 2 and 13 block DPP-4; C-20… Subcutaneous half-life 5 d.
Synthetic 39-residue dual agonist at GLP-1R + GIP-R. Aib substitutions at positions 2 and 13 block DPP-4; C-20 fatty diacid on Lys-20 binds albumin → ~5-day t½. Biased toward GIP-R cAMP signalling over β-arrestin recruitment. SURMOUNT-1: −20.9% weight loss at 72 weeks (15 mg) — largest weight-loss magnitude of any approved pharmacotherapy at trial time.
PK: Schneck 2024 (PMID:38356317), population model over 19 pooled studies, verbatim "The half-life of tirzepatide was ~5 days" = 120 h; the stored 116 h appears nowhere. Corroborated independently by Furihata 2022 (PMID:34647404), 48 Japanese participants, "approximately 5 days". V 9.1 L and ka 0.04 /h dropped 2026-09-06 — no PubMed abstract states a tirzepatide volume of distribution at all, so there is nothing to re-source to. PK: ABSORPTION RATE AUTHORED FROM THE MOUNJARO LABEL. This row carried no ka, so the solver substituted 1.0/h and put the peak at 5.2 h. Source, verbatim from the current FDA label (DailyMed setid d2d7da5d-ad07-4228-955f-cf7e355c8cc0): "Following subcutaneous administration, the time to maximum plasma concentration of tirzepatide ranges from 8 to 72 hours." RANGE, and an unusually wide one: the shorter endpoint is taken. 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 0.5825/h, which reproduces 8 h on substitution. EXPOSURE IS UNCHANGED: the absorption rate cancels out of AUC, so only the shape moves.
Pharmacokinetics
- Subcutaneous — t½ 5.0 d · ka 0.5825 h⁻¹
Sources: PMID:38356317, PMID:35658024, PMID:30473097, PMID:34647404