Drug metabolism and interactions in abuse liability assessment.

The interpretation of acute abuse liability studies and drug interaction studies would be importantly strengthened by the routine inclusion of drug concentration measurements at appropriate sampling times. Reliance on mean kinetic data misrepresents the variation in drug kinetics and fails to take experimental advantage of the natural differences in the population which may represent the extremes of abuse risk. Pharmacokinetic-pharmacodynamic studies to better understand the relationship of plasma drug concentration, drug concentration in the receptor biophase and specific drug reinforced behaviour will ensure proper study design and yield useful theoretic information. Multi- and poly-drug abuse (including heavy smoking and heavy ethanol use) are very common. Such patterns of use can have quite large effects on drug kinetics. Because of the potentially large qualitative and quantitative differences in drug metabolism and kinetics between pre-clinical species and the human, data should be gathered at the earliest possible time with respect to human metabolic rates, patterns, and identification of inhibitors. The availability of human liver microsomes facilitates such studies.