Valaciclovir (BW256U87): The L-valyl ester of acyclovir

Abstract

Valaciclovir (BW256U87) is an L‐valyl ester of acyclovir, which is extensively and almost completely converted to acyclovir. In healthy human volunteers, single valaciclovir doses of 100–1000 mg resulted in dose‐proportional increases in acyclovir area under the curve (AUC). The 1,000 mg dose produced an acyclovir peak plasma concentration (Cmax) of 5–6 μg/ml, AUC₆ of 19 hr .μg/ml, time to maximum plasma concentration (Tmax) of 1–2 hr, and half‐life (T_1/2) of 2.8 hr. Plasma valaciclovir peak levels were 6 = 30.5 hr . ug/ml, and T_1/2 = 3.3 hr. Nausea, vomiting, diarrhoea, and abdominal pain were commonly reported; however, only one adverse event (diarrhoea) was causally linked to valaciclovir exposure. There were no renal or neurologic adverse events. Valaciclovir is well absorbed and is rapidly converted to acyclovir, resulting in three‐ to fourfold higher acyclovir levels than can be achieved with oral acyclovir, even in patients with advanced HIV disease. The safety profile is generally favourable, with no evidence of nephrotoxicity or neurotoxicity.