Comparative metabolism as a key driver of wildlife species sensitivity to human and veterinary pharmaceuticals

Show simple item record Hutchinson, Thomas H. Madden, Judith C. Naidoo, Vinny Walker, Colin H. 2015-07-27T08:19:36Z 2015-07-27T08:19:36Z 2014-10
dc.description.abstract Human and veterinary drug development addresses absorption, distribution, metabolism, elimination and toxicology (ADMET) of the Active Pharmaceutical Ingredient (API) in the target species. Metabolism is an important factor in controlling circulating plasma and target tissue API concentrations and in generating metabolites which are more easily eliminated in bile, faeces and urine. The essential purpose of xenobiotic metabolism is to convert lipid-soluble, non-polar and non-excretable chemicals into water soluble, polar molecules that are readily excreted. Xenobiotic metabolism is classified into Phase I enzymatic reactions (which add or expose reactive functional groups on xenobiotic molecules), Phase II reactions (resulting in xenobiotic conju-gation with large water-soluble, polar molecules) and Phase III cellular efflux transport processes. The human–fish plasma model provides a useful approach to understanding the pharmacokinetics of APIs (e.g. diclofenac, ibu-profen and propranolol) in freshwater fish, where gill and liver metabolism of APIs have been shown to be of importance. By contrast, wildlife species with low metabolic competency may exhibit zero-order metabolic (pharmacoki-netic) profiles and thus high API toxicity, as in the case of diclofenac and the dramatic decline of vulture populations across the Indian subcontinent. A similar threat looms for African Cape Griffon vultures exposed to ketoprofen and meloxicam, recent studies indicating toxicity relates to zero-order metabolism (suggesting P450 Phase I enzyme system or Phase II glucuronida-tion deficiencies). While all aspects of ADMET are important in toxicity evaluations, these observations demonstrate the importance of methods for predicting API comparative metabolism as a central part of environmental risk assessment. en_ZA
dc.description.embargo 2015-10-31 en_ZA
dc.description.librarian hb2015 en_ZA
dc.description.uri en_ZA
dc.identifier.citation Hutchinson, TH, Madden, JC, Naidoo, V & Walker, CH 2014, 'Comparative metabolism as a key driver of wildlife species sensitivity to human and veterinary pharmaceuticals', Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, vol. 369, art. #20130583, pp. 1-9. en_ZA
dc.identifier.issn 0080-4622 (print)
dc.identifier.issn 2054-0280 (online)
dc.identifier.other 10.1098/rstb.2013.0583
dc.identifier.other A-1508-2008
dc.identifier.other 8621439700
dc.language.iso en en_ZA
dc.publisher Royal Society en_ZA
dc.rights © The Royal Society 2014 en_ZA
dc.subject Medicines en_ZA
dc.subject Environment en_ZA
dc.subject Exposure en_ZA
dc.subject Birds en_ZA
dc.subject Fish en_ZA
dc.subject Invertebrates en_ZA
dc.title Comparative metabolism as a key driver of wildlife species sensitivity to human and veterinary pharmaceuticals en_ZA
dc.type Postprint Article en_ZA

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