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The behavioral effects of a drug are related to three factors: its intrinsic pharmacological activity, its physicochemical properties, and its pharmacokinetic parameters. In many cases differences in absorption, distribution, metabolism, and elimination may explain the different abuse liability profiles of drugs from within the same pharmacological class. Rapid absorption rate and high lipid solubility are the most important factors contributing to early drug concentrations in the brain. Differences in drug metabolism may be related to dose-dependent kinetics, first-pass metabolism, and variations in genetic traits (e.g. poor or extensive metabolizers). Metabolic pathways may produce active metabolites with similar or greater pharmacological activity than the parent substance. Drugs with a rapid elimination rate have been associated with greater self-administration and with early emergence of withdrawal symptoms. More pharmacokinetic studies are needed in human drug abuse liability evaluations. Knowledge of the plasma concentrations of drugs and their pharmacokinetic parameters can be essential to interpret differences among similar drugs in human abuse liability assessments. [ABSTRACT FROM AUTHOR]

Testing of drugs for abuse liability can benefit public health. By encouraging proper therapeutic use, appropriate regulation, and development of safer and more effective drugs, such testing can benefit both consumers and pharmaceutical manufacturers. Many factors influence actual abuse; animal and human drug abuse liability testing procedures are useful, though imperfect, predictors of abuse. Three suggestions are made concerning human drug abuse liability testing: (1) that more research is needed on differences between individuals and between different subpopulations tested with these procedures (2) that actual epidemiological experience concerning abuse should be the 'gold standard' for assessing the validity and utility of drug abuse liability testing methods; and (3) that methods for drug abuse liability testing in humans should be introduced and used systematically to guide appropriate development, regulation, and marketing of drugs. [ABSTRACT FROM AUTHOR]