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Mu-opioid receptor (A118G) single-nucleotide polymorphism affects alfentanil requirements for extracorporeal shock wave lithotripsy: a pharmacokinetic–pharmacodynamic study

2009; Elsevier BV; Volume: 103; Issue: 3 Linguagem: Inglês

10.1093/bja/aep192

1471-6771

Yehuda Ginosar, Elyad Davidson, Yuval Meroz, Simcha Blotnick, M. Shacham, Y. Caraco,

Opioid Use Disorder Treatment

BackgroundThere are diverse reports concerning the single-nucleotide polymorphism (SNP) A118G in the gene coding for the mu-opioid receptor. This study assessed pharmacokinetic–pharmacodynamic relationships in patients with acute pain (water-immersed extracorporeal shock wave lithotripsy).MethodsNinety-nine patients (ASA I–II, age 18–70) were assessed in this prospective observational study. Blinding was achieved by determining genotype only after the procedure. I.V. alfentanil was administered by patient-controlled administration (loading dose, 10 µg kg−1; continuous infusion, 20 µg kg−1 h−1; bolus, 3 µg kg−1; lockout time, 1 min); no other analgesic or sedating medication was used.ResultsThe allelic frequency was 15.2% in our population. The G118 SNP (AG/GG) was associated with a 27% increase in plasma alfentanil concentration (P=0.034), a 54% increase in alfentanil dose (P=0.009), a 47% increase in dose per kg body weight (P=0.004), a 55% increase in dose per kg corrected for stimulus intensity (P=0.002), a 112% increase in the numbers of attempted boluses (P=0.015), a 79% increase in the numbers of successful boluses (P=0.013), and a 153% increase in the numbers of failed boluses (P=0.042). Despite the increased alfentanil self-administration, the G118 SNP was associated with a 52% increase in verbal analogue pain scores over the same period of time (P=0.047).ConclusionsWe demonstrated increased opioid requirement for alfentanil in patients with the G118 SNP, who self-administered a higher dose, achieved higher plasma concentration, and yet complained of more severe pain. This observation suggests that G118 SNP impairs the analgesic response to opioids. There are diverse reports concerning the single-nucleotide polymorphism (SNP) A118G in the gene coding for the mu-opioid receptor. This study assessed pharmacokinetic–pharmacodynamic relationships in patients with acute pain (water-immersed extracorporeal shock wave lithotripsy). Ninety-nine patients (ASA I–II, age 18–70) were assessed in this prospective observational study. Blinding was achieved by determining genotype only after the procedure. I.V. alfentanil was administered by patient-controlled administration (loading dose, 10 µg kg−1; continuous infusion, 20 µg kg−1 h−1; bolus, 3 µg kg−1; lockout time, 1 min); no other analgesic or sedating medication was used. The allelic frequency was 15.2% in our population. The G118 SNP (AG/GG) was associated with a 27% increase in plasma alfentanil concentration (P=0.034), a 54% increase in alfentanil dose (P=0.009), a 47% increase in dose per kg body weight (P=0.004), a 55% increase in dose per kg corrected for stimulus intensity (P=0.002), a 112% increase in the numbers of attempted boluses (P=0.015), a 79% increase in the numbers of successful boluses (P=0.013), and a 153% increase in the numbers of failed boluses (P=0.042). Despite the increased alfentanil self-administration, the G118 SNP was associated with a 52% increase in verbal analogue pain scores over the same period of time (P=0.047). We demonstrated increased opioid requirement for alfentanil in patients with the G118 SNP, who self-administered a higher dose, achieved higher plasma concentration, and yet complained of more severe pain. This observation suggests that G118 SNP impairs the analgesic response to opioids.