Applied Pharmacokinetics in Drug Development

The process of discovering, developing, and marketing new drugs has changed considerably in the last decade; however, the cost associated with this process remains staggeringly high. Although there are many reasons for this high cost, one reason appears to be the continuing high attrition rates of drugs during costly early- and late-stage human clinical trials. To address this problem, drug discovery organizations are striving to rapidly identify high-potential drug candidates and eliminate as early as possible those with inferior potency, poor pharmacokinetic properties, and toxicity problems, so that these deficient drug candidates do not incur the high costs of clinical trials. During the last 5 years, a decision-making go/no-go strategy has been introduced into the drug discovery process, using pharmacokinetic principles to minimize the risks and maximize the benefits of selecting superior drug candidates. Pharmacological deficiencies are related in part to pharmacokinetic properties. To understand this process, a brief review of pharmacokinetic properties including oral bioavailability, half-life, absorption, clearance, and volume of distribution is presented. We examine in vitro — in vivo (human) and/or in vivo (animals) — in vivo (human) correlations for several of these pharmacokinetic properties, followed by a discussion of how this preclinical information is collected and used in drug discovery at the various stages to select drug candidates. Finally, we summarize how these methods are used to make go/no-go decisions in each step of the drug discovery process.