Comparative bioavailability of acyclovir from oral valacyclovir and acyclovir in patients treated for recurrent genital herpes simplex virus infection.

The bioavailabilities of acyclovir from capsules of valacyclovir, the L-valyl ester of acyclovir, and acyclovir were compared by measuring urinary excretion of the drug in a double blind, placebo-controlled field trial of patient-initiated treatment for recurrent genital herpes. Forty-six healthy patients with recurrent genital herpesvirus infection were randomly assigned to receive acyclovir 200 mg five times daily (n=20), valacyclovir 1000 mg twice daily (equivalent to 694 mg acyclovir twice daily) (n=18) or placebo (n=6). Thirty-three patients on the active treatments provided the required 24 h urine samples for assessment of bioavailability. The acyclovir treatment group excreted 267+/-178 mg (mean +/- SD), and the valacyclovir treatment group excreted 623+/-248 mg (mean +/- SD) acyclovir over 24 h. The mean acyclovir bioavailabilities, estimated from urinary acyclovir excretion, were 26.7+/-17.8% and 44.9+/-17.9% for acyclovir and valacyclovir, respectively (P<0.007). There was no effect of sex on acyclovir bioavailability with either drug. The relative mean bioavailability of acyclovir was 68% greater from the prodrug formulation. This field trial in patients who self-initiated treatment for recurrent genital herpes confirmed that the prodrug valacyclovir provided significantly greater acyclovir bioavailability than the parent drug, as initially shown in volunteers in clinical pharmacokinetic studies.

RCT Entities:   Population Interventions Outcomes