title: Skin pigmentation and pharmacokinetics of melanotan-I in humans.
abstract: A comparative pharmacokinetic trial was performed with a superpotent synthetic melanotropic peptide, [Nle4-D-Phe7]-alpha-MSHi-13 (melanotan-I or MT-I) given by three routes of administration. Plasma levels were measured by RIA and tanning was quantiated using serial reflectometry. Doses of 0.16 mgkg-1 were administered intravenously (IV) and orally (PO), and doses from 0.08 to 0.21 mg kg-1 subcutaneously (SC), in a randomized crossover fashion to three male volunteers over five consecutive days for 2 weeks (ten doses). The results indicate that the SC dose is completely bioavailable compared to the IV dose. No detectable drug levels were observed following PO dosing. The plasma half-lives following SC dosing ranged from 0.07 to 0.79 h for the absorption phase and from 0.8 to 1.7 h for the beta-phase. Clearance ranged from 0.12 to 0.19 L kg-1 h-1 and 3.9% or less of the dose was recovered in the urine. Side-effects were minimal, consisting of occasional gastrointestinal upset and facial flushing. Significant tanning of the forehead, arms, and neck was noted following IV or SC dosing. This effect peaked at 1 week following drug administration but was still present 3 weeks after completing the ten-dose regimen. It is concluded that SC administration is an efficacious method of delivering melanotan-I.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona 85721, USA.
authors.forename: S O
authors.initials: SO
authors.lastname: Ugwu
authors.forename: J
authors.initials: J
authors.lastname: Blanchard
authors.forename: R T
authors.initials: RT
authors.lastname: Dorr
authors.forename: N
authors.initials: N
authors.lastname: Levine
authors.forename: C
authors.initials: C
authors.lastname: Brooks
authors.forename: M E
authors.initials: ME
authors.lastname: Hadley
authors.forename: M
authors.initials: M
authors.lastname: Aickin
authors.forename: V J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000284:Administration, Oral; D000328:Adult; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D011863:Radioimmunoassay; D012880:Skin Pigmentation / Q000187:drug effects*; D044465:White People; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D016588:Anticarcinogenic Agents; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-