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

Br J Anaesth. 2009 Sep;103(3):420-7. doi: 10.1093/bja/aep192. Epub 2009 Jul 15.


Background: 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).

Methods: 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 microg kg(-1); continuous infusion, 20 microg kg(-1) h(-1); bolus, 3 microg kg(-1); lockout time, 1 min); no other analgesic or sedating medication was used.

Results: 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).

Conclusions: 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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alfentanil / administration & dosage*
  • Alfentanil / adverse effects
  • Alfentanil / blood
  • Analgesia, Patient-Controlled / methods
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / blood
  • Drug Administration Schedule
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Lithotripsy / adverse effects*
  • Male
  • Middle Aged
  • Pain / etiology
  • Pain / genetics
  • Pain Measurement / methods
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Receptors, Opioid, mu / genetics*
  • Sex Factors
  • Young Adult


  • Analgesics, Opioid
  • Receptors, Opioid, mu
  • Alfentanil