Kongara K
Animal Welfare Science and Bioethics Centre, Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
J Vet Pharmacol Ther. 2018 Apr;41(2):195-204. doi: 10.1111/jvp.12452. Epub 2017 Sep 11.
Genetic variation causes interindividual variability in drug absorption, distribution, metabolism and excretion. These pharmacokinetic processes will influence the observed efficacy and toxicity of a drug. Polymorphisms in the genes encoding the metabolizing enzymes, transport proteins and receptors have been linked to the inconsistency in responses to opioid treatment in humans and laboratory animals. Pharmacogenetics is relatively less developed field in veterinary medicine compared to significant advances in knowledge on genetic basis of variation in drug responses and clinical applications in human medicine. This review discusses the opioid drug metabolism and possible genetic polymorphism of metabolizing enzymes in dogs. Polymorphism of genes encoding opioid drug transporter proteins and its effect on opioid response and opioid receptor gene variants are also discussed. Due to the scarcity of studies reported on opioid pharmacogenetics in dogs, relevant studies in humans and rodents have also been discussed to indicate current trends and potential targets for research in dogs.
基因变异导致个体间在药物吸收、分布、代谢和排泄方面存在差异。这些药代动力学过程会影响所观察到的药物疗效和毒性。编码代谢酶、转运蛋白和受体的基因中的多态性与人类和实验动物对阿片类药物治疗反应的不一致有关。与人类医学在药物反应变异的遗传基础和临床应用方面的重大进展相比，药物遗传学在兽医学领域的发展相对滞后。本综述讨论了犬类阿片类药物代谢以及代谢酶可能存在的基因多态性。还讨论了编码阿片类药物转运蛋白的基因多态性及其对阿片类药物反应的影响以及阿片类受体基因变异。由于关于犬类阿片类药物遗传学的研究报道较少，因此也讨论了人类和啮齿动物的相关研究，以指出犬类研究的当前趋势和潜在研究靶点。
