Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota.
Clin Gastroenterol Hepatol. 2019 Mar;17(4):584-594. doi: 10.1016/j.cgh.2018.04.052. Epub 2018 Apr 27.
The objectives are to review the role of pharmacogenomics in drug metabolism of medications typically used in patients with irritable bowel syndrome (IBS) focusing predominantly on cytochrome P450 metabolism. Other aims are to provide examples of genetic variation of receptors or intermediary pathways that are targets for IBS drugs and to critically appraise the situations where precision medicine is impacting health in IBS. Pharmacogenomics impacts both pharmacokinetics and pharmacodynamics. Although large clinical trials have not incorporated testing for genetic variations that could impact the efficacy of medications in IBS, there are therapeutic advantages to inclusion of pharmacogenomics testing for individual patients, as has been demonstrated particularly in the treatment with central neuromodulators in psychiatry practice. Clinical practice in IBS is moving in the same direction with the aid of commercially available tests focused on drug metabolism. Specific mechanisms leading to pathophysiology of IBS are still poorly characterized, relative to diseases such as cancer and inflammatory bowel disease, and, therefore, pharmacogenomics related to drug pharmacodynamics is still in its infancy and requires extensive future research. With increased attention to pharmacogenomics affecting drug metabolism, it is anticipated that pharmacogenomics will impact care of IBS.
目的是回顾药物代谢遗传学在肠易激综合征(IBS)患者常用药物中的作用,主要集中在细胞色素 P450 代谢上。其他目的是提供 IBS 药物的受体或中间途径的遗传变异的例子,并批判性地评价精准医学在 IBS 中影响健康的情况。药物代谢遗传学既影响药代动力学又影响药效动力学。尽管大型临床试验尚未纳入可能影响 IBS 药物疗效的遗传变异测试,但为个别患者进行药物代谢遗传学测试具有治疗优势,这在精神病学实践中使用中枢神经调节剂的治疗中得到了特别证明。在商业上可用于药物代谢检测的帮助下,IBS 的临床实践正在朝着相同的方向发展。与癌症和炎症性肠病等疾病相比,导致 IBS 病理生理学的具体机制仍知之甚少,因此,与药物药效动力学相关的药物代谢遗传学仍处于起步阶段,需要进行广泛的未来研究。随着对影响药物代谢的药物代谢遗传学的关注增加,预计药物代谢遗传学将影响 IBS 的护理。