Topical Iontophoresis of Valaciclovir Hydrochloride Improves Cutaneous Aciclovir Delivery

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


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


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 (∼0.06%) formulation was 20 ± 10, 104 ± 47 and 194 ± 82 μg cm−2, respectively (cf. non-quantifiable levels, 0.1 and 1.0 ± 0.7 μg cm−2 after ACV iontophoresis).


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.

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