Valacyclovir

Valacyclovir (Valaciclovir) is an orally active antiviral drug for herpes simplex, herpes zoster, and herpes B. Valacyclovir inhibits HSV-1 W (₅₀=2.9 μg/ml). Valacyclovir is a prodrug of Aciclovir (HY-17422) ^{[1][2][3][4][5]}. In Vitro: Valacyclovir (Valaciclovir; VACV) uptake was concentration dependent and saturable with a Michaelis-Menten constant and maximum velocity of 1.64 mM and 23.34 nmol/mg protein/5 min, respectively. A very similar Km value was obtained in hPEPT1/CHO cells and in rat and rabbit tissues and Caco-2 cells, suggesting that hPEPT1 dominates the intestinal transport properties of VACV in vitro^[5]. In Vivo: For treatment of a first episode of genital herpes, a large comparative trial has shown that Valacyclovir (1 g twice a day) is as effective as acyclovir (200 mg five times a day) when given for 10 days. For treating recurrences, two trials show that valacyclovir is as effective as acyclovir (200 mg five times a day) with a treatment period of 5 days. A daily dose of 1 g of valacyclovir is as effective as 2 g daily. Valacyclovir can be administered once a day^[1].
The concentrations of acyclovir in serum and CSF were measured at steady state after 6 days of oral treatment with 1,000 mg of valacyclovir three times a day^[2].
EC50 values of PE and AC in 3T3 cells were 0.02 and 0.01 ug/ml, while values in BHK cells were 0.2 and 0.03 ug/ml. Treatment of infected immunosuppressed mice and FA and VA (b.i.d., 5.5 days) reduced the proportion with erythema from 100% to 24% and 38%, and eliminated ear paralysis, ear lesions (vesicles, etc) and death. Virus was absent from ear and brainstem by day 6, but reappeared after discontinuation in mice treated with VA^[3].