The μ-opioid receptor gene polymorphism 118A>G weakens the pharmacological action of buprenorphine.

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).