Imai Hiromitsu, Morita Misaki, Morita Hajime, Ohyama Tetsuji, Tanaka Shimako, Uchida Shinya, Namiki Noriyuki, Uemura Naoto, Ohashi Kyoichi
Int J Clin Pharmacol Ther. 2020 Nov;58(11):626-633. doi: 10.5414/CP203755.
Opioids are commonly used analgesics for moderate to severe pain, but levels of drug effect vary among individuals. As for the mechanisms underlying these individual differences, there have been reports suggesting effects of polymorphisms in the gene encoding μ-opioid receptor (). However, whether these polymorphisms affect the actions of μ-opioid receptor partial agonists has yet to be determined. This study aimed to assess differences in the pharmacological actions of buprenorphine, a μ-opioid receptor partial agonist, due to a polymorphism (A118G, rs1799971) in the gene in humans.
Ten healthy adult men (5 with c.118AA and 5 with c.118GG) received a single intravenous dose of buprenorphine hydrochloride at 0.001 mg/kg. Blood samples were collected up to 360 minutes after drug administration to assess the pharmacokinetics of buprenorphine. Nociceptive thresholds (temperature), digital symbol substitution test (DSST), and visual analog self-rating scale (VAS) for subjective symptoms were also evaluated over time to assess the pharmacodynamics.
Nociceptive thresholds were significantly increased in the AA as compared to the GG group after buprenorphine administration (p = 0.025), while the DSST scores were significantly lower in the AA group (p < 0.001). The VAS scores for drowsiness (p < 0.001), malaise (p < 0.001), nausea (p < 0.001), and euphoria (p = 0.004) were higher in the AA than in the GG group.
Levels of pharmacological actions of a μ-opioid receptor partial agonist vary in accordance with a polymorphism in the gene (A118G).
阿片类药物是常用于治疗中度至重度疼痛的镇痛药，但个体间药物效应水平存在差异。至于这些个体差异背后的机制，有报告表明编码μ-阿片受体（ ）的基因多态性具有影响。然而，这些多态性是否影响μ-阿片受体部分激动剂的作用尚未确定。本研究旨在评估人类 基因中的一种多态性（A118G，rs1799971）导致的μ-阿片受体部分激动剂丁丙诺啡药理作用的差异。
10名健康成年男性（5名 c.118AA型和5名 c.118GG型）静脉注射0.001mg/kg的盐酸丁丙诺啡单次剂量。给药后360分钟内采集血样以评估丁丙诺啡的药代动力学。还随时间评估伤害性感受阈值（温度）、数字符号替换测试（DSST）以及主观症状的视觉模拟自评量表（VAS），以评估药效学。
与GG组相比，丁丙诺啡给药后AA组的伤害性感受阈值显著升高（p = 0.025），而AA组的DSST评分显著更低（p < 0.001）。AA组的嗜睡（p < 0.001）、不适（p < 0.001）、恶心（p < 0.001）和欣快感（p = 0.004）的VAS评分高于GG组。
μ-阿片受体部分激动剂的药理作用水平因 基因中的多态性（A118G）而异。
