Abstract

Aims: 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 (OPRM1). 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 OPRM1 gene in humans.
Materials and methods: Ten healthy adult men (5 with OPRM1 c.118AA and 5 with OPRM1 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.
Results: 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.
Conclusion: Levels of pharmacological actions of a μ-opioid receptor partial agonist vary in accordance with a polymorphism in the OPRM1 gene (A118G).

Author Details

Authors

• Hiromitsu Imai^{1, 2}
• Misaki Morita²
• Hajime Morita²
• Tetsuji Ohyama³
• Shimako Tanaka⁴
• Shinya Uchida⁴
• Noriyuki Namiki⁴
• Naoto Uemura²
• Kyoichi Ohashi²

Departments

• ¹ Department of Medical Ethics,
• ² Department of Clinical Pharmacology and Therapeutics, Oita University Faculty of Medicine, Hasama-machi, Yufu-city, Oita, 
• ³ Biostatistics Center, Kurume University, Kurume-city, Fukuoka, and
• ⁴ Department of Pharmacy Practice and Science, School of Pharmaceutical Sciences, University of Shizuoka, Suruga, Shizuoka-city, Shizuoka, Japan

Address

Hiromitsu Imai, MD, PhD
Department of Medical Ethics
Oita University Faculty of Medicine
1-1 Idaigaoka Hasama-machi,
Yufu-city, Oita, 879-5593, Japan
Email: [email protected]

Citation