TRANSDERMAL PERMEATION OF ALNIDITAN BY IONTOPHORESIS - IN-VITRO OPTIMIZATION AND HUMAN PHARMACOKINETIC DATA

Purpose, The aim of this paper was to assess the feasibility of electr ically enhanced transdermal delivery of alniditan, a novel 5 HT1D agon ist for the treatment of migraine. Methods. An in vitro study was firs t performed to optimize the different parameters affecting iontophores is efficiency. The mechanism of alniditan permeation by iontophoresis was investigated. Finally, a phase I clinical trial was performed to a ssess systemic delivery of alniditan by iontophoresis. Results, i) In vitro; The optimal conditions were found with a buffer like ethanolami ne at a pH of 9.5, with Ag/AgCl electrodes and a direct current applic ation. Alniditan permeation was enhanced when increasing the current d ensity, the duration of current application and the drug concentration . Iontophoresis slightly increased drug quantities in stratum corneum compared to passive diffusion but it strongly increased alniditan quan tities in viable skin. ii) The objective to deliver in vivo 0.5 mg of alniditan within less than 1 h was reached but an erythema was detecte d at the anode. Conclusions. This study demonstrates the feasibility o f iontophoretic delivery system for antimigraine compounds.