Abstract |
Melanotan-II (1) is a cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone ( alpha-MSH) which tans the skin and is currently being evaluated for the prevention of sunlight-induced skin cancers. The dissociation constants of 1 were determined using potentiometric titration and ultraviolet spectrophotometry. The pKa1 ( histidine) and pKa2 ( arginine) were estimated to be 6.54 and 11.72, respectively. The apparent partition coefficient (PC) was measured at three pH values using both n-octanol and isooctane as the nonpolar phase. The PC(octanol) and delta log PC at pH 7.35 were 2.82 and 1.05, respectively. These data, together with the observance of a bioavailability of 4.6% in the rat, indicate that 1 may be a suitable candidate for oral delivery. The data presented here are useful in developing an appropriate dosage form for 1.
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Authors | E L Lan, S O Ugwu, J Blanchard, X Fang, V J Hruby, S Sharma |
Journal | Journal of pharmaceutical sciences
(J Pharm Sci)
Vol. 83
Issue 8
Pg. 1081-4
(Aug 1994)
ISSN: 0022-3549 [Print] United States |
PMID | 7983590
(Publication Type: Journal Article)
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Chemical References |
- Anticarcinogenic Agents
- Peptides, Cyclic
- melanotan-II
- alpha-MSH
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Topics |
- Amino Acid Sequence
- Animals
- Anticarcinogenic Agents
(administration & dosage, chemistry, pharmacokinetics)
- Biological Availability
- Chemical Phenomena
- Chemistry, Physical
- Hydrogen-Ion Concentration
- Molecular Sequence Data
- Peptides, Cyclic
(administration & dosage, chemistry, pharmacokinetics)
- Potentiometry
- Rats
- Skin Neoplasms
(prevention & control)
- Spectrophotometry, Ultraviolet
- alpha-MSH
(administration & dosage, analogs & derivatives, chemistry, pharmacokinetics)
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