Topical iontophoresis of valaciclovir hydrochloride improves cutaneous aciclovir delivery.
OBJECTIVE
To investigate the topical iontophoresis of valaciclovir (VCV) as a means to improve cutaneous aciclovir (ACV) delivery.


METHODS
ACV and VCV electrotransport experiments were conducted using excised porcine skin in vitro.


RESULTS
While the charged nature of the prodrug, VCV, enabled it to be more efficiently iontophoresed into the skin than the parent molecule, ACV, only the latter was detectable in the receptor chamber, suggesting that VCV was enzymatically cleaved into the active metabolite during skin transit. Iontophoresis of VCV was significantly more efficient than that of ACV; the cumulative permeation of ACV after 1, 2 and 3 h of VCV iontophoresis at 0.5 mA cm(-2) and using an aqueous 2 mM (approximately 0.06%) formulation was 20+/-10, 104+/-47 and 194+/- 82 microg cm( -2), respectively (cf. non-quantifiable levels, 0.1 and 1.0+/-0.7 microg cm(-2) after ACV iontophoresis).


CONCLUSIONS
These delivery rates provide ample room to reduce either current density or the duration of current application. Preliminary in vitro data serve to emphasize the potential of VCV iontophoresis to improve the topical therapy of cutaneous herpes simplex infections and merit further investigation to demonstrate clinical efficacy.
Abla
Nada
N
School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, 1211 Geneva, Switzerland.
Naik
Aarti
A
Guy
Richard H
RH
Kalia
Yogeshvar N
YN
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000287:Administration, Topical; D000465:Algorithms; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007478:Iontophoresis; D051379:Mice; D008812:Mice, Hairless; D011355:Prodrugs; D011817:Rabbits; D012869:Skin Absorption / Q000502:physiology*; D013056:Spectrophotometry, Ultraviolet; D013552:Swine; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D000998:Antiviral Agents; D011355:Prodrugs; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir