The clinical pharmacology of acyclovir and its prodrugs

Acyclovir (Zovirax) is a highly specific antiherpes virus agent. Extensive investigations of the pharmacokinetics in man have shown it to have a useful half-life of about three hours and to be largely excreted unchanged in the urine. Crystaluria can be avoided provided the patient is well hydrated and attention is paid to the dosing instructions especially in patients with renal failure. In vitro ED50s (the drug concentration inhibiting virus replication by 50%) bear some general relevance to effective plasma levels in man. A new prodrug of acyclovir, 2-amino-9-[2-hydroxyethoxy methyl]-9H-purine (A515U), which is converted to acyclovir by xanthine oxidase is rapidly absorbed from the human gut and converted to acyclovir. This prodrug provides the opportunity to design regimes that are more convenient for the patient and may be more effective than acyclovir itself in the therapy of the less sensitive herpes viruses (e.g. Epstein-Barr virus and the Cytomegalovirus).