Pharmacology, Tolerance, and Antiviral Activity of Vidarabine Monophosphate in Humans

Abstract

Vidarabine (adenine arabinoside) is a purine nucleoside useful in humans for therapy of herpes simplex virus encephalitis and herpes zoster virus infections in immunocompromised patients. The potential usefulness of vidaribine is limited by its poor solubility, which requires continuous infusion in relatively large volumes of i.v. fluid. Vidarabine 5''-monophosphate is highly soluble and has the advantage that it can be administered intermittently i.m. or i.v. In a clinical, pharmacokinetic study, plasma levels and urinary excretion of vidarabine 5''-monophosphate were determined after i.v. and i.m. administration in 29 immunosuppressed patients with herpes simplex or zoster virus infections at dosages of 15-30 mg/kg per day administered for 5 days. As determined by high-pressure liquid chromatography, vidarabine 5''-monophosphate was metabolized in a fashion comparable to the metabolism of vidarabine and its major metabolite in plasma was arabinosyl hypoxanthine. After administration, 40-50% of the vidarabine 5''-monophosphate was recovered from the urine as arabinosyl hypoxanthine, and 3-4% was recovered as vidarabine. Determinations of areas under the curve for arabinosyl hypoxanthine were not statistically different by dosage for i.m. or i.v. routes of administration. At all dosages studied, viral clearance appeared to occur with therapy. The advantage of increased solubility will lead to controlled clinical investigations in which vidarabine 5''-monophosphate is administered by i.m. or i.v. routes against targeted human herpesvirus infections.