Cytochrome P450 3A4 genetic polymorphisms and post-operative fentanyl requirements.
OBJECTIVE
Interindividual variability in drug responses may be attributable to genetically determined alteration in enzyme activity. In this study, we investigated the association between cytochrome P450 3A4 (CYP3A4) genetic polymorphisms and post-operative fentanyl requirements.


METHODS
Patients (n = 94) scheduled for gynaecological laparotomy received i.v. fentanyl infusion (3 μg/kg/h) after induction of general anaesthesia. Post-operative fentanyl requirements were quantified by using a patient-controlled analgesia and the number of i.v. fentanyl rescue analgesia required were recorded. Pain control was assessed using visual analogue scores (VAS) and fentanyl's adverse effects were documented. CYP3A4*4, CYP3A4*5 and CYP3A4*18 alleles of cytochrome P450 3A4 were identified by polymerase chain reaction-restriction fragment length polymorphism. Differences in fentanyl requirements, VAS scores and adverse effects among the various genotypes were compared.


CONCLUSIONS
No CYP3A4*4 and CYP3A4*5 alleles were detected. Eighty-nine patients (94·7%) were wild-type, five (5·3%) were heterozygous and none was homozygous. No significant difference was demonstrated between the genotype groups in terms of fentanyl consumption, pain control and adverse effects.


CONCLUSIONS
CYP3A4*4 and CYP3A4*5 are rare in the Malaysian Malay population. Genetic polymorphism of CYP3A4*18 may not play an important role in influencing postoperative fentanyl requirements.
Department of Anaesthesiology and Intensive Care, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
P C S
PC
Tan
S K
SK
Hassan
N A N
NA
Mohamad
S H
SH
Gan
D000328:Adult; D016058:Analgesia, Patient-Controlled / Q000379:methods; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000627:therapeutic use*; D005838:Genotype; D013509:Gynecologic Surgical Procedures / Q000379:methods; D006801:Humans; D007262:Infusions, Intravenous; D007813:Laparotomy / Q000379:methods; D008296:Malaysia; D008875:Middle Aged; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy* / Q000201:enzymology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D000701:Analgesics, Opioid; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D005283:Fentanyl