Preclinical Toxicology Studies with Acyclovir: Ophthalmic and Cutaneous Tests

Species Differences in the Metabolism and Disposition of Antiviral Nucleoside Analogues: 1. Acyclovir

“…Application of 1cm ribbon of a 3% ACV ophthalmic ointment (approx 21 mg) to the rabbit cornea resulted in significant ACV levels in the aqueous humour within 0.5h and mean peak levels of 0.57 fLg mr' at 2h post-treatment. The corresponding mean plasma ACV level was 0.14 fL9 mr', indicating that there was some systemic delivery of the drug after topical corneal application (Tucker et al, 1983a). In a different study, instillation of a higher dose of ointment (42mg) in the rabbit cul-desac resulted in peak ACV levels in aqueous humour and the cornea of 3.38 and 45.8fL9 mr ", respectively.…”

“…In guinea pigs, topical appliation of a 5% ACV ointment in abraded skin resulted in mean plasma ACV levels of 0.06 fLg rnr' after a single dose, and 0.71 fL9 mr' after multiple doses (Tucker et al, 1983a). Mean plasma levels were 0.18 and 0.86 fL9 mr' after single and multiple doses, respectively, one hour after application of a 10% ointment to the intact skin.…”

Nail Loss and Footpad Erosions in Beagle Dogs Given BW 134U, a Nucleoside Analog

“…Other lesions that were considered related to treatment with the mid and high doses of BW 134U were similar to those recorded for acyclovir (14) and included thymic involution, focal mucosal hypoplasia of the esophagus, and subacute enteritis secondary to epithelial maturation defects in crypt epithelium of all portions of the gastrointestinal tract.…”

“…Visual inspection revealed congestion and a small amount of hemorrhage in the area of the claw fold before the nails were actually shed. The female was necropsied on postdose day 14 tions (nail bed area) of the denuded ungual processes of the claws. There were no gross lesions in the paws of mid dose dogs, but several foot pads had superficial erosions and moderate acanthosis when examined by light microscopy.…”

Influence of drug loading and type of ointment base on the in vitro performance of acyclovir ophthalmic ointment

“…In this study, the influence of three ointment bases (oleaginous, absorption and water soluble bases) on the in vitro performance (IVRT and IVPT) was studied. The ingredients used for the bases are approved for ophthalmic use and showed minimal irritation when applied on rabbit eyes (CIRExpertPanel, 2006;FDA;Fruijtier-Polloth, 2005;Tucker et al, 1983). Water washable bases were eliminated from the study because of the possible eye irritation of hydrophilic surfactants such as lauryl sulfate that are required for the formulation.…”