Transdermal permeation of alniditan by iontophoresis: in vitro optimization and human pharmacokinetic data.
OBJECTIVE
The aim of this paper was to assess the feasibility of electrically enhanced transdermal delivery of alniditan, a novel 5 HT1D agonist for the treatment of migraine.


METHODS
An in vitro study was first performed to optimize the different parameters affecting iontophoresis efficiency. The mechanism of alniditan permeation by iontophoresis was investigated. Finally, a phase I clinical trial was performed to assess systemic delivery of alniditan by iontophoresis.


RESULTS
i) In vitro: The optimal conditions were found with a buffer like ethanolamine at a pH of 9.5, with Ag/AgCl electrodes and a direct current application. Alniditan permeation was enhanced when increasing the current density, 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 quantities 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 detected at the anode.


CONCLUSIONS
This study demonstrates the feasibility of iontophoretic delivery system for antimigraine compounds.
Jadoul
A
A
Université Catholique de Louvain, Ecole de Pharmacie, Unité de Pharmacie Galénique, Brussels, Belgium.
Mesens
J
J
Caers
W
W
de Beukelaar
F
F
Crabbé
R
R
Préat
V
V
D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D001578:Benzopyrans / Q000493:pharmacokinetics*; D002021:Buffers; D004566:Electrodes; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods*; D008297:Male; D011437:Propylamines / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000493:pharmacokinetics*; D051381:Rats; D012869:Skin Absorption; D014662:Vasoconstrictor Agents / Q000493:pharmacokinetics* / Q000494:pharmacology
D001578:Benzopyrans; D002021:Buffers; D011437:Propylamines; D011743:Pyrimidines; D014662:Vasoconstrictor Agents; C100822:alniditan