title: In vitro species comparisons and metabolite identification.
abstract: The metabolism and elimination of a drug has a direct bearing on its potential to cause toxicity in humans as well as to influence its clinical activity. The confidence with which data from preclinical safety studies, particularly toxicology studies, can be extrapolated to humans depends upon knowing whether humans are exposed to the same chemical entities (i.e., a parent drug and its metabolites) as the laboratory animals used to study toxicity and pharmacological responses. To address this issue, the FDA Guidance for Industry (1997) recommends the use of in vitro interspecies metabolic comparisons at an early stage in the drug development process. Knowledge about the metabolism of a compound is also important from a drug discovery perspective. In vitro studies provide a convenient and cost-effective way to obtain this information. This unit presents protocols for comparing metabolite profiles across several species, as well as methods for identifying metabolites.
authors.affiliation: Covance Laboratories, Inc., Madison, Wisconsin, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Dow
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry; D000882:Haplorhini; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008862:Microsomes, Liver / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011868:Radioisotopes; D051381:Rats; D013045:Species Specificity; D013048:Specimen Handling / Q000379:methods; D013739:Testosterone / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations; D011868:Radioisotopes; D013739:Testosterone