Feline Drug Metabolism and Disposition

Court, Michael H.

doi:10.1016/j.cvsm.2013.05.002

Cited by 112 publications

(59 citation statements)

References 65 publications

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“…cats) and birds (e.g. raptors) eat very little, if any, plant material and therefore do not incur major pressure to drive the evolution of enzymes to metabolize plant toxins [17][18][19][20]. Interestingly, zebrafish (a widely used model in pharmaceutical research) show a dramatic increase in Phase I and II enzyme activity at the juvenile life stage in association with being fed plant-based diets [21].…”

Section: Introductionmentioning

confidence: 99%

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

Hutchinson

Madden

Naidoo

et al. 2014

Phil. Trans. R. Soc. B

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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 conjugation 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, ibuprofen 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 (pharmacokinetic) 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 glucuronidation 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.

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Section: Introductionmentioning

confidence: 99%

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

Hutchinson

Madden

Naidoo

et al. 2014

Phil. Trans. R. Soc. B

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“…B 370: 20140233 Table 1 [119]. Cats are recognized as being extremely sensitive to azathioprine and have lower red blood cell TPMT activity compared with dogs and humans [120,121]. Additional research in companion animals and other non-human species will build on preliminary research and explore the functional and clinical impact of TPMT polymorphisms to help identify altered drug responses, ultimately improving animal models in drug development [119,120,122].…”

Section: What Role Do Interspecies Differences Inmentioning

confidence: 99%

Species differences in tumour responses to cancer chemotherapy

Lawrence

Cameron

Argyle

2015

Phil. Trans. R. Soc. B

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Despite advances in chemotherapy, radiotherapy and targeted drug development, cancer remains a disease of high morbidity and mortality. The treatment of human cancer patients with chemotherapy has become commonplace and accepted over the past 100 years. In recent years, and with a similar incidence of cancer to people, the use of cancer chemotherapy drugs in veterinary patients such as the dog has also become accepted clinical practice. The poor predictability of tumour responses to cancer chemotherapy drugs in rodent models means that the standard drug development pathway is costly, both in terms of money and time, leading to many drugs failing in Phase I and II clinical trials. This has led to the suggestion that naturally occurring cancers in pet dogs may offer an alternative model system to inform rational drug development in human oncology. In this review, we will explore the species variation in tumour responses to conventional chemotherapy and highlight our understanding of the differences in pharmacodynamics, pharmacokinetics and pharmacogenomics between humans and dogs. Finally, we explore the potential hurdles that need to be overcome to gain the greatest value from comparative oncology studies.

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“…All target species, also carry out conjugation reactions with sulfate and glucuronic acid (Watkins and Klaassen, 1986;James, 1987;Gusson et al, 2006), producing water-soluble derivatives that are eliminated in urine. The FEEDAP Panel notes that for feline species the capacity for conjugation is limited (Court, 2013 and Krajkeman, 1967). Study reports for these compounds are not available and the FEEDAP Panel is unable to confirm the no observed adverse effect levels (NOAELs) derived.…”

Section: Safetymentioning

confidence: 99%

Safety and efficacy of pyrazine derivatives including saturated ones belonging to chemical group 24 when used as flavourings for all animal species

Additives¹,

Rychen²,

Aquilina³

et al. 2017

EFS2

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Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of 22 compounds belonging to chemical group 24 (pyrazine derivatives). [14.126] are safe at the proposed maximum dose level (0.5 mg/kg complete feed) as feed for cattle, salmonids and non-food-producing animals, and at the proposed normal use level of 0.1 mg/kg complete feed for pigs and poultry; 5-methylquinoxaline [14.028] are safe only at concentrations below the proposed use levels (0.08 mg/kg complete feed for cattle, salmonids and nonfood-producing animals, and 0.05 mg/kg complete feed for pigs and poultry). No safety concern would arise for the consumer from the use of these compounds up to the highest proposed level in feeds. Hazards for skin and eye contact, and respiratory exposure are recognised for the majority of the compounds under application. Most are classified as irritating to the respiratory system. The proposed maximum use levels in feed are unlikely to have detrimental effects on the terrestrial and fresh water compartments. Because all the compounds under assessment are used in food as flavourings and their function in feed is essentially the same as that in food, no further demonstration of efficacy is necessary.

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Feline Drug Metabolism and Disposition

Cited by 112 publications

References 65 publications

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

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

Species differences in tumour responses to cancer chemotherapy

Safety and efficacy of pyrazine derivatives including saturated ones belonging to chemical group 24 when used as flavourings for all animal species

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