Preclinical Development of Antiviral Drugs

The early preclinical development of an antiviral agent is accomplished essentially in two stages. The first stage consists of gathering data to estimate the potential therapeutic index of the agent. This process includes testing for antiviral activity and for cytotoxicity in vitro and performing preliminary pharmacokinetic and toxicology studies in vivo. The second stage consists of carrying out more-extensive safety (toxicology) studies to determine any significant potential toxicities before the agent is used in humans. Chronic-toxicity studies, reproductive toxicity studies, and carcinogene-sis bioassays are performed to support clinical trials of longer duration and, ultimately, approval of efficacious antiviral agents. It is essential to identify toxicities early in the developmental process for both safety and economic reasons. Progress in determining the mechanisms of specific toxicities will greatly aid in risk assessment and in our ability to predict and avoid these toxicities. The preclinical development of an antiviral agent includes all the testing and evaluation of a compound, culminating in the filing of an investigational new drug (IND) application with the U.S. Food and Drug Administration and the initia-tion of clinical trials. An important component of this pro