Pharmacology, Tolerance, andAntiviral Activity ofVidarabine Monophosphate inHumans

patients. However, thepotential usefulness ofvidaribine is limited byits poor solubility, whichrequires continuous infusion inrelatively large volumes ofintravenous fluid. Vidarabine 5'-monophosphate ishighly soluble andhastheadvantage thatitcanbeadministered intermittently intramuscularly orintravenously. Ina clinical, pharmacokinetic study, plasma levels andurinary excretion ofvidarabine 5'-monophosphate were determined after intravenous and intramuscular administration in29immunosuppressed patients withherpes simplex orzoster virus infections atdosages of15to30mg/kgperdayadministered for5days. Asdetermined byhigh-pressure liquid chromatography, vidarabine 5'monophosphate was metabolized ina fashion comparable tothemetabolism of vidarabine anditsmajormetabolite inplasma was arabinosyl hypoxanthine. After administration, 40to50%ofthevidarabine 5'-monophosphate was recovered fromtheurine as arabinosyl hypoxanthine, and3 to4% was recovered as vidarabine. Determinations ofareasunderthecurveforarabinosyl hypoxanthine were notstatistically different bydosage forintramuscular orintravenous routes ofadministration. Atalldosages studied, viral clearance appeared tooccur with therapy. Theadvantage ofincreased solubility will leadtocontrolled clinical investigations inwhichvidarabine 5'-monophosphate isadministered byintramuscular orintravenous routes against targeted humanherpesvirus infections. Thedevelopment ofvidarabine (vira-A) asan antiviral agent hasstimulated theintroduction ofpromising compounds forclinical evaluation. Asnewtherapeutic agents aredeveloped, pharmacokinetic andtolerance studies mustprecede drugefficacy evaluations. Ideally, these studies canprovide information regarding theoptimal routeofdrugadministration, plasma levels at defined dosages, half-life, metabolism, clearance, anddegree ofpenetration intocerebrospinal fluid. Inaddition, preliminary dataregarding viral clearance andtoxicity areobtained. Anorderly approach tothestudy ofantiviral