Drug metabolism and interactions in abuse liability assessment. 1991

E M Sellers, and S V Otton, and U E Busto
Department of Pharmacology, University of Toronto, Canada.

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.

UI MeSH Term Description Entries
D011619 Psychotropic Drugs A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). Psychoactive Agent,Psychoactive Agents,Psychoactive Drug,Psychopharmaceutical,Psychopharmaceuticals,Psychotropic Drug,Psychoactive Drugs,Agent, Psychoactive,Agents, Psychoactive,Drug, Psychoactive,Drug, Psychotropic,Drugs, Psychoactive,Drugs, Psychotropic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004341 Drug Evaluation Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. Evaluation Studies, Drug,Drug Evaluation Studies,Drug Evaluation Study,Drug Evaluations,Evaluation Study, Drug,Evaluation, Drug,Evaluations, Drug,Studies, Drug Evaluation,Study, Drug Evaluation
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012307 Risk Factors An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, based on epidemiological evidence, is known to be associated with a health-related condition considered important to prevent. Health Correlates,Risk Factor Scores,Risk Scores,Social Risk Factors,Population at Risk,Populations at Risk,Correlates, Health,Factor, Risk,Factor, Social Risk,Factors, Social Risk,Risk Factor,Risk Factor Score,Risk Factor, Social,Risk Factors, Social,Risk Score,Score, Risk,Score, Risk Factor,Social Risk Factor
D019966 Substance-Related Disorders Disorders related to substance use or abuse. Chemical Dependence,Drug Abuse,Drug Addiction,Drug Dependence,Drug Habituation,Drug Use Disorder,Drug Use Disorders,Organic Mental Disorders, Substance-Induced,Substance Abuse,Substance Dependence,Substance Related Disorder,Substance Use,Substance Use Disorder,Substance Use Disorders,Prescription Drug Abuse,Substance Addiction,Abuse, Drug,Abuse, Prescription Drug,Abuse, Substance,Addiction, Drug,Addiction, Substance,Chemical Dependences,Dependence, Chemical,Dependence, Drug,Dependence, Substance,Dependences, Chemical,Disorder, Drug Use,Disorder, Substance Related,Disorder, Substance Use,Disorders, Substance Related,Drug Abuse, Prescription,Habituation, Drug,Organic Mental Disorders, Substance Induced,Related Disorder, Substance,Related Disorders, Substance,Substance Abuses,Substance Uses,Use, Substance

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