Evaluation of four antiviral agents in the treatment of herpes simplex encephalitis in a rat model.

Three hundred four animals were used for the systematic evaluation of the in vivo efficacy of 5-iodo-2'-deoxyuridine (IUDR), cytosire arabinoside, 9-beta-arabinofuranosyladenine, and isoprinosine in the therapy of herpes simplex encephalitis in an adult rat model. Type 1 herpes simplex virus was inoculated intracerabrally, and drug was administered by the intraperitoneal route. All experiments included tests for toxicity and viral controls, Eight sets of experiments were used for evaluation of ttherapy with IUDR; the inoculum ranged from 64 to 2,000 TCID50, dose of drug from 0.1 mg/g to 1.0 mg/g per day, and duration of therapy from one to five days. There was no significant improvement in the number of animals surviving or in the survival time when the viral controls were compared with mice in treated groups. A slight trend toward increased survival time and decreased titer of virus in the brains of animals treated with IUDR was noted in the group that received the largest dose. Three or four sets of experiments were used to evaluate each of the other three antiviral drugs. Results were similar to those reported for IUDR. These results indicate a need for further studies, including investigations of the pharmacology and toxicity of these antiviral agents, to establish more clearly the dosages of drug that are therapeutic, those that are toxic, and ratios of these dosages.