Lee Pamela M, Faus Michele C L, Court Michael H
Program in Individualized Medicine (PrIMe), Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington.
J Vet Pharmacol Ther. 2019 Jan;42(1):16-25. doi: 10.1111/jvp.12717. Epub 2018 Sep 24.
Clopidogrel response variability has been identified in cats. In humans, evidence suggests that variable clopidogrel active metabolite (CAM) generation is the primary explanation for clopidogrel response variability with differences in body weight, sex, and variable metabolism of clopidogrel primarily due to polymorphisms of the gene encoding cytochrome P450 (CYP) 2C19 as some proposed mechanisms. The aim of this study was to evaluate whether variation in CAM concentrations exists in healthy cats and what the cause of such variation might be. Nineteen healthy cats were given 18.75 mg clopidogrel by mouth. Blood was collected 2 hr later. Plasma CAM concentrations were measured using high performance liquid chromatography and tandem mass spectrometry. Clopidogrel metabolism was estimated by calculating CAM metabolic ratio. DNA was collected, and feline CYP2C genotyping was performed. The cats demonstrated high interindividual variation of plasma CAM concentrations. Approximately 69% of this interindividual variation was primarily explained by differences in clopidogrel metabolism as measured by CAM metabolic ratio with some influence by sex but not by weight. A single nucleotide polymorphism was identified in the feline CYP2C gene that explained in part individual differences in CAM metabolic ratio and CAM plasma concentrations.
已在猫身上发现氯吡格雷反应变异性。在人类中，有证据表明，氯吡格雷活性代谢物（CAM）生成的差异是氯吡格雷反应变异性的主要原因，其差异主要体现在体重、性别方面，以及氯吡格雷代谢的差异，主要是由于编码细胞色素P450（CYP）2C19的基因多态性等一些推测机制。本研究的目的是评估健康猫体内CAM浓度是否存在差异，以及这种差异的原因可能是什么。19只健康猫口服18.75毫克氯吡格雷。2小时后采集血液。使用高效液相色谱和串联质谱法测量血浆CAM浓度。通过计算CAM代谢率来评估氯吡格雷的代谢情况。采集DNA，并进行猫CYP2C基因分型。这些猫表现出血浆CAM浓度的高度个体间差异。这种个体间差异中约69%主要由CAM代谢率所衡量的氯吡格雷代谢差异所解释，性别有一定影响，但体重无影响。在猫CYP2C基因中鉴定出一个单核苷酸多态性，部分解释了CAM代谢率和CAM血浆浓度的个体差异。
