Abstract

The development of new drugs for life threatening diseases is an expensive, risky and time-consuming endeavour. Each new marketed drug costs an estimated $1.2bn to develop. The chances of a molecule making it to Phase I--where drugs are traditionally administered to humans for the first time--out of discovery are no more than one in 5000. And a molecule entering Phase I has only a one in ten chance of making it through to registration.

Drugs can fail development for various reasons, including lack of clinical efficacy, toxicity in animal models and toxic side effects. Predicting these effects has proved difficult. What we do know, however, is the importance of human drug metabolism and pharmacokinetics (PK) in selecting successful drug candidates.

Pharmacokinetics is the mathematical descriptor of a drug's absorption, distribution, metabolism and excretion (ADM E), which is closely related to its efficacy and toxicity. Knowing about a drug's metabolism is probably the second most important property that needs to be understood after its pharmacology.