Afamelanotide

peptide · integumentary · endocrine · Subcutaneous

Afamelanotide, a peptide. Linear 13-residue alpha-MSH analogue (Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2). The Nle4… Subcutaneous half-life 0.8 h.

Linear 13-residue alpha-MSH analogue (Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2). The Nle4 and D-Phe7 substitutions resist enzymatic degradation and raise potency far above the native hormone, while keeping MC1R as the dominant target — so unlike melanotan-ii next door this is a SELECTIVE melanocortin-1 agonist, not a pan-MCR agonist. MC1R signalling increases eumelanin synthesis, induces antioxidant activity, enhances DNA repair and modulates inflammation. Approved by the EMA in 2014 as a 16 mg controlled-release subcutaneous implant for preventing phototoxicity in erythropoietic protoporphyria, which makes it the only approved drug in the melanotan family and the reason it must not be confused with the grey-market MT-II.

PubChem CID 16197727 (C78H111N21O19). ALL FOUR PK PARAMETERS COME FROM ONE PAPER, Ugwu 1997 (PMID:9113347), three male volunteers given ten doses by three routes in a randomised crossover. F = 1 is verbatim in Ugwu (PMID:9113347): "the SC dose is completely bioavailable compared to the IV dose". Corroborated by Minder 2017 (PMID:28063031), "Subcutaneous application had full bioavailability". HALF-LIFE 0.8 h is the LOWER ENDPOINT of "from 0.8 to 1.7 h for the beta-phase" — an endpoint rather than the midpoint, per this catalog's standing rule; the upper endpoint would roughly double the exposure duration. ka 9.9021 /h is a UNIT CONVERSION, not a back-derivation: the paper states an absorption-phase half-life "from 0.07 to 0.79 h", and ln2/0.07 = 9.9021. The LOWER endpoint is used there for a reason worth keeping: 0.79 h gives ka 0.8774 /h against this record's ke of 0.8664 /h, a 1.3% difference, and ka-ke sits in the Bateman denominator — that corner of the range is not representable in a one-compartment model at all. VOLUME IS A DECLARED DERIVATION. No Cmax, AUC or Vd is published for this drug by any route, but the abstract states "Clearance ranged from 0.12 to 0.19 L kg-1 h-1", and CL with t-half fixes V: (0.12 x 70) / (ln2/0.8) = 8.4 / 0.8664340 = 9.6949 L. The record therefore reproduces a verbatim published clearance by construction. Storing nothing was the alternative and it is worse: a missing V_L asserts the solver default of 0.5 L/kg = 35 L, and the band this paper permits is 9.7-32.6 L across the two ranges, so the default sits above ALL of it and would have run every curve up to 3.6x low. The clearance sentence does not name a route, which is normally where route mismatch creeps in; it cannot here, because complete SC bioavailability makes CL and CL/F the same number. Resolved through resolvePk at 11.2 mg this record peaks at 0.915 mg/L (555 nmol/L) at 16 min — a disclosed prediction, not a measurement, since no Cmax exists to check it against. DOSE BLOCK IS THE INJECTION, NOT THE IMPLANT. The cited study dosed 0.08-0.21 mg/kg SC with a 0.16 mg/kg point dose in the IV and PO arms; those are stored as 70 kg equivalents (5.6-14.7 mg, typical 11.2) because DoseUnit has no weight-based member and the solver never weight-scales. THE MARKETED PRODUCT IS A DIFFERENT KINETIC OBJECT: a 16 mg controlled-release implant every 60 days (PMID:26132941, two phase III trials), whose release profile is zero-order over weeks and is NOT published. Melanin density after one implant "increased by day 7, peaked at day 15 and remained elevated at day 60" (PMID:20969564) — pharmacodynamics, not kinetics. Logging 16 mg against this record renders the INJECTION curve and will be wrong by orders of magnitude in duration; that is in AUTHORING_GAPS as the open item. ORAL IS DEAD ON PURPOSE: "No detectable drug levels were observed following PO dosing", so PO is not a listed route. Mechanism references PMID:11237737 and PMID:8605020 (MC1R binding and signalling).

Pharmacokinetics

Related compounds

Sources: PMID:9113347, PMID:28063031, PMID:26132941, PMID:20969564, PMID:11237737, PMID:8605020