BJA Advance Access originally published online on July 15, 2009
British Journal of Anaesthesia 2009 103(3):420-427; doi:10.1093/bja/aep192
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Mu-opioid receptor (A118G) single-nucleotide polymorphism affects alfentanil requirements for extracorporeal shock wave lithotripsy: a pharmacokinetic–pharmacodynamic study
1 Department of Anesthesiology and Critical Care Medicine and
2 Clinical Pharmacology Unit, Division of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel
* Corresponding author. E-mail: edavidson{at}hadassah.org.il
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 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.
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.
Keywords: analgesia, patient-controlled; genetic factors; pharmacodynamics; pharmacokinetics, alfentanil; receptors, opioid
These authors contributed equally to this study.