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Because drug transporters play an important role in drug absorption, distribution, and excretion, alterations in drug transporter function can result in adverse drug reactions.
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The ABCB1 polymorphism in dogs and drug interactions involving P-glycoprotein can enhance the toxicity of many drugs.
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The species-wide ABCG2 defect in cats is responsible for fluoroquinolone-induced retinal toxicity.
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Because drug transporters play an important role in drug disposition, a thorough understanding of drug
Veterinary Clinics of North America: Small Animal Practice
Adverse Drug Reactions in Veterinary Patients Associated with Drug Transporters
Section snippets
Key points
ATP-binding cassette superfamily
There are more than 40 members of the ABC protein superfamily. These proteins use ATP to transport substrates across biological membranes (often against steep concentration gradients). Substrates for ABC transporters include ions, peptides, hormones, conjugated metabolites, and xenobiotics, including drugs.1 Only 3 members of the ABC transporter superfamily are known to transport drug molecules as their substrates: P-glycoprotein (P-gp) (encoded by the ABCB1, formerly MDR1, gene); breast cancer
Solute carrier superfamily
The SLC superfamily of transporters uses several different processes (facilitated diffusion, ion coupling, ion exchange) to transport substrates across biological membranes. Some members of the SLC superfamily are uptake transporters (transport substrates into cells) whereas others are efflux transporters (transport substrates out of cells).1 In humans and rodents, members of the SLC superfamily mediate transport of a variety of structurally diverse compounds, including endogenous and exogenous
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Cited by (19)
Complications of chemotherapy agents
2022, Small Animal Critical Care MedicineAntifungal Drugs
2022, Greene's Infectious Diseases of the Dog and Cat, Fifth EditionMetabolism and pharmacokinetics of pharmaceuticals in cats (Felix sylvestris catus) and implications for the risk assessment of feed additives and contaminants
2021, Toxicology LettersCitation Excerpt :Also hepatic MRP2 (ABCC2), which participates in biliary excretion of chemicals, does not seem to be expressed in cats (Malekinejad et al., 2015). Overall, the above-mentioned deficiencies are expected to decrease the elimination rate of several chemicals possibly resulting in drug toxicity (Mealey, 2013). Further research is needed to assess the impact of transporters on the kinetics of pharmaceuticals and toxicants in cats and other feline species.
Papich Handbook of Veterinary Drugs: Small and Large Animal
2020, Papich Handbook of Veterinary Drugs: Small and Large AnimalCanine gastrointestinal physiology: Breeds variations that can influence drug absorption
2015, European Journal of Pharmaceutics and BiopharmaceuticsCitation Excerpt :Clearly, GI physiology is only one of many factors that can influence in vivo drug bioavailability. Much variability is also known to exist in liver and gut metabolizing enzymes, as well as transporter activity [78–81]. All these additional factors are capable of influencing the response to pharmaceutical interventions.
Drug-drug interactions: An evolving science in need of experimental models and systems
2014, Veterinary Journal
Disclosures: Dr Mealey and Washington State University hold the patent for MDR1 genotyping and receive royalties for MDR1 genotyping services.