Transdermal iontophoretic delivery of vapreotide acetate across porcine skin in vitro.
OBJECTIVE
The purpose of this study was to evaluate the feasibility of delivering vapreotide, a somatostatin analogue, by transdermal iontophoresis.


METHODS
In vitro experiments were conducted using dermatomed porcine ear skin and heat-separated epidermis. In addition to quantifying vapreotide transport into and across the skin, the effect of peptide delivery on skin permselectivity was also measured. The influence of (1) current density, (2) pre- and post-treatment of the skin, (3) competitive ions, and (4) inclusion of albumin in the receptor on vapreotide delivery were investigated.


RESULTS
Epidermis proved to be a better model than dermatomed skin for vapreotide transport studies. Despite the susceptibility of vapreotide to enzymatic degradation, a flux of 1.7 microg/cm2 per hour was achieved after 7 h of constant current iontophoresis (0.15 mA/cm2). Post-iontophoretic extraction revealed that, depending on the experimental conditions, 80-300 microg of peptide were bound to the skin. Vapreotide was found to interact with the skin and displayed a current-dependent inhibition of electroosmosis. However, neither the pre-treatment strategies to saturate the putative binding sites nor the post-treatment protocols to displace the bound peptide were effective.


CONCLUSIONS
Based on the observed transport rate of vapreotide across porcine epidermis and its clinical pharmacokinetics, therapeutic concentrations should be achievable using a 15-cm2 patch.
Schuetz
Yannic B
YB
School of Pharmaceutical Sciences, University of Geneva, Geneva, CH-1211, Switzerland.
Naik
Aarti
A
Guy
Richard H
RH
Vuaridel
Evelyne
E
Kalia
Yogeshvar N
YN
D000082:Acetaminophen / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000494:pharmacology; D004817:Epidermis / Q000378:metabolism; D066298:In Vitro Techniques; D007478:Iontophoresis; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013552:Swine
D018712:Analgesics, Non-Narcotic; D000970:Antineoplastic Agents; D002593:Cetrimonium Compounds; C051458:vapreotide; D000082:Acetaminophen; D013004:Somatostatin; D000077286:Cetrimonium