Overview of in vitro metabolism of drugs by aquatic species.
Most of the major pathways of drug metabolism have been studied in vitro in liver of one or more fish species using model compounds as substrates, but there have been few studies of the metabolism of specific drugs. The cytochrome P-450 dependent monooxygenase system has been studied in many fish species from waters of different temperatures and salinities, and there are numerous quantitative differences between fish species in their ability to catalyze the oxidation of model compounds. In all fish species studied to date, treatment with chemicals of the polyaromatic hydrocarbon type have caused induction of the oxidative metabolism of the expected substrates, whereas treatment with phenobarbital and related chemicals has not induced oxidative metabolism. Cytochrome P-450 dependent monooxygenase activity has been demonstrated in several invertebrate species. Varying carboxylesterase activities have been found in liver and extrahepatic organs of fish, and these may result in differing susceptibilities to ester drugs which are inactivated by hydrolysis. Of the conjugation pathways, glutathione conjugation of electrophilic chemicals, glycosylation of phenols and alcohols, and taurine conjugation of carboxylic acids have been studied in vitro in aquatic animals, but there have been few or no studies of sulfotransferases or acetyltransferases. Considerable species differences are found in levels of activity for most of the pathways studied, and it is therefore not possible at present to predict how a new drug will be metabolized by aquatic animals, based on available literature.
James
M O
MO
Department of Medicinal Chemistry, University of Florida, Gainesville 32610.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D005399:Fishes / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000502:physiology; D005982:Glutathione Transferase / Q000502:physiology; D006867:Hydrolases / Q000502:physiology; D066298:In Vitro Techniques; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D006867:Hydrolases