Passage of somatostatin analogue across human and mouse skin.
Recent studies have documented beneficial effects of the somatostatin analogue, SMS 201-995 (hereafter referred to as SMS), when administered subcutaneously to patients with a variety of disorders. Since SMS is a small peptide, we tested the ability of two penetrant enhancers--dimethylsulfoxide and N-decylmethylsulfoxide (C10MS)--to promote transcutaneous passage of SMS. Samples of skin from human cadavers and hairless mice were tested in a static diffusion chamber. Application of SMS in conjunction with 1% C10MS resulted in rapid transdermal passage of SMS. These data were confirmed for hairless mouse skin in experiments with a modified diffusion chamber having continuous flow-through of receptor fluid in the subdermal reservoir. In this system, the cumulative amount of SMS that permeated hairless mouse skin was 20 micrograms/cm2/24 hours. Topical application of SMS with C10MS beneath a patch to mice confirmed in vitro data. Topical application of 10 micrograms of SMS resulted in plasma SMS levels of greater than 8,000 pg/ml within 2 hours. We conclude that SMS will cross both human and mouse skin, with a clinically significant flux, when administered topically with C10MS. The data support the feasibility of in vivo human trials of topical SMS therapy.
D000279:Administration, Cutaneous; D000818:Animals; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008851:Micropore Filters; D015282:Octreotide; D012867:Skin / Q000378:metabolism*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
C054274:1-decyl methyl sulfoxide; D013004:Somatostatin; D015282:Octreotide; D004121:Dimethyl Sulfoxide