Biomaterial Database

In vitro approaches to evaluate ADMET drug properties. 2004

Albert P Li

Advanced Pharmaceutical Sciences, Inc, PMB#146, 6400 Baltimore National Pike, Baltimore, MD 21228, USA. lialbert@apsciences.com

In vitro assays developed for the evaluation of drug-like properties can accelerate the drug development process. The key assays are those for the evaluation of bioavailability, metabolic stability, drug-drug interaction potential, and toxicity. For bioavailability, the human colon carcinoma derived Caco-2 assay is the most widely used, allowing the evaluation of multiple pathways of intestinal absorption including paracellular uptake, transcellular uptake, and transporter-mediated uptake and efflux. For metabolic stability and drug-drug interactions, human liver microsomes, hepatocytes, and cDNA-expressed microsomes are commonly used, with human hepatocytes representing the most complete system, containing all metabolic enzymes and cofactors at physiological level and an intact plasma membrane to allow the modeling of intracellular drug concentrations. Primary human cells from target organs (e.g., human hepatocytes for human hepatotoxicity) should represent the best experimental system for the evaluation of human drug toxicity. These assays, when applied intelligently with their limitations, should greatly facilitate the selection of drug candidates with a high probability of clinical success.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
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
D004353	Drug Evaluation, Preclinical	Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.	Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D004355	Drug Stability	The chemical and physical integrity of a pharmaceutical product.	Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D004364	Pharmaceutical Preparations	Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.	Drug,Drugs,Pharmaceutical,Pharmaceutical Preparation,Pharmaceutical Product,Pharmaceutic Preparations,Pharmaceutical Products,Pharmaceuticals,Preparations, Pharmaceutical,Preparation, Pharmaceutical,Preparations, Pharmaceutic,Product, Pharmaceutical,Products, Pharmaceutical
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001682	Biological Availability	The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.	Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D015195	Drug Design	The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis.	Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D064420	Drug-Related Side Effects and Adverse Reactions	Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.	Drug-Related Side Effects and Adverse Reaction,Adverse Drug Event,Adverse Drug Reaction,Drug Side Effects,Drug Toxicity,Side Effects of Drugs,Toxicity, Drug,Adverse Drug Events,Adverse Drug Reactions,Drug Event, Adverse,Drug Events, Adverse,Drug Reaction, Adverse,Drug Reactions, Adverse,Drug Related Side Effects and Adverse Reaction,Drug Related Side Effects and Adverse Reactions,Drug Side Effect,Drug Toxicities,Effects, Drug Side,Reactions, Adverse Drug,Side Effect, Drug,Side Effects, Drug,Toxicities, Drug