Naito Takafumi, Kawakami Junichi
Department of Hospital Pharmacy, Hamamatsu University School of Medicine.
Yakugaku Zasshi. 2015;135(5):709-15. doi: 10.1248/yakushi.14-00234-4.
Use of prescription opioids for cancer pain according to the World Health Organization analgesic ladder has been accepted in Japan. Although oxycodone and fentanyl are commonly used as first-line analgesics, a few clinical reports have been published on interindividual variations in their pharmacokinetics and clinical responses in cancer patients. (1) Some factors relating to CYP2D6, CYP3A, ATP-binding cassette sub-family B member 1 (ABCB1), and opioid receptor mu 1 (OPRM1) involve oxycodone pharmacokinetics and sensitivity in humans. The relations between their genetic variations and clinical responses to oxycodone are being revealed in limited groups. In our study, the impact of genetic variants and pharmacokinetics on clinical responses to oxycodone were evaluated in Japanese populations. (2) Opioid switching improves the opioid tolerance related to the balance between analgesia and adverse effects. Some patients have difficulty in obtaining better opioid tolerance in recommended conversion ratios. The activities of CYP3A, ABCB1, and OPRM1 contribute to the interindividual variations in clinical responses to fentanyl in cancer patients. However, the variations in opioid switching remain to be clarified in clinical settings. In our study, genetic factors related to interindividual variations in clinical responses in opioid switching to fentanyl were revealed in Japanese populations. In this symposium review, the possibility of approaches to personalized palliative care using opioids based on genetic variants of CYP2D6, CYP3A5, ABCB1, and OPRM1 is discussed.
根据世界卫生组织镇痛阶梯使用处方阿片类药物治疗癌症疼痛在日本已被接受。尽管羟考酮和芬太尼通常用作一线镇痛药，但关于癌症患者中它们的药代动力学和临床反应的个体差异，仅有少数临床报告发表。（1）一些与细胞色素P450 2D6（CYP2D6）、细胞色素P450 3A（CYP3A）、ATP结合盒转运体B家族成员1（ABCB1）和阿片受体μ1（OPRM1）相关的因素涉及羟考酮在人体内的药代动力学和敏感性。它们的基因变异与羟考酮临床反应之间的关系正在有限的人群中被揭示。在我们的研究中，在日本人群中评估了基因变异和药代动力学对羟考酮临床反应的影响。（2）阿片类药物转换可改善与镇痛和不良反应平衡相关的阿片类药物耐受性。一些患者难以按照推荐的转换比例获得更好的阿片类药物耐受性。CYP3A、ABCB1和OPRM1的活性导致癌症患者对芬太尼临床反应的个体差异。然而，阿片类药物转换中的差异在临床环境中仍有待阐明。在我们的研究中，在日本人群中揭示了与阿片类药物转换为芬太尼时临床反应个体差异相关的遗传因素。在本次研讨会综述中，讨论了基于CYP2D6、CYP3A5、ABCB1和OPRM1基因变异使用阿片类药物进行个性化姑息治疗的方法的可能性。
