Skin Pigmentation and Pharmacokinetics of Melanotan-I in Humans

✍ Scribed by SYDNEY O. UGWU; JAMES BLANCHARD; ROBERT T. DORR; NORMAN LEVINE; CHRISTINE BROOKS; MAC E. HADLEY; MIKEL AICKIN; VICTOR J. HRUBY

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 152 KB
• Volume: 18
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199704)18:3<259::aid-bdd20>3.0.co;2-x

✦ Synopsis

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.