Mu-opioid receptor (A118G) single-nucleotide polymorphism affects alfentanil requirements for extracorporeal shock wave lithotripsy: a pharmacokinetic-pharmacodynamic study.
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.
Ginosar
Y
Y
Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Davidson
E M
EM
Meroz
Y
Y
Blotnick
S
S
Shacham
M
M
Caraco
Y
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D015760:Alfentanil / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016058:Analgesia, Patient-Controlled / Q000379:methods; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008096:Lithotripsy / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology / Q000235:genetics; D010147:Pain Measurement / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012737:Sex Factors; D055815:Young Adult
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D015760:Alfentanil