Setmelanotide
Setmelanotide, a peptide. MC4R-selective melanocortin agonist — restores hypothalamic POMC pathway signaling in genetic obesity from… Subcutaneous half-life 11 h.
MC4R-selective melanocortin agonist — restores hypothalamic POMC pathway signaling in genetic obesity from POMC, PCSK1, LEPR, or BBS deficiency. FDA-approved for these specific monogenic obesities + Bardet-Biedl syndrome. Hyperpigmentation + erection (MC1R + MC4R cross) are class effects. PK (Imcivree label, 3 mg SC qd SS): Apparent V/F 75.2 L, effective t½ ~11 h, total apparent CL/F 7.15 L/h (typical 120 kg male, normal renal function). Free fraction ~0.2. SC bioavailability lower than IV due to interstitial protease/peptidase degradation + lymphatic clearance — F 0.85 estimated (label notes "lower than IV" without quoting; consistent with other small-peptide SC depots). Metabolized to small peptides by general catabolic pathways. First MC4R agonist approved for monogenic obesity (POMC/PCSK1/LEPR deficiency, BBS).
PK stays on the approval document, which is legitimate primary provenance here: no PubMed-indexed study reports a setmelanotide half-life, volume, absorption rate or bioavailability, so there is nothing to re-source to. Corrections applied 2026-09-06: the stored volume was 75 against the document's stated 75.2, a silent rounding of a cited figure; F 0.85 is removed because no bioavailability appears in that document at all, and pairing it with an explicitly APPARENT V/F double-counted absorption; F is pinned to 1 for that reason. ka 0.2 /h removed — the only absorption statement is a median time to peak of 8 h.
Pharmacokinetics
- Subcutaneous — t½ 11 h · F 100% · Vd 75.2 L