Patient-controlled analgesia (PCA) with codeine for postoperative pain relief in ten extensive metabolisers and one poor metaboliser of dextromethorphan.
Postoperative pain relief with codeine was evaluated in 11 women undergoing hysterectomy. Patient-controlled analgesia (PCA) was used to administer codeine. After the study the patients were phenotyped with respect to the O-demethylation of dextromethorphan (cytochrome P4502D6 polymorphism). Ten were extensive metabolisers and one a poor metaboliser. There was a nine-fold variation in the minimum plasma concentration of codeine consistent with pain relief (40-350 ng ml-1). Two patients did not experience any effect of codeine, one of whom was a poor metaboliser of dextromethorphan, confirmed by genotyping. In the other nine patients the effective dose of codeine varied from 4.8-25.3 mg h-1.
Persson
K
K
Department of Clinical Pharmacology, Akademiska Hospital, Uppsala, Sweden.
Sjöström
S
S
Sigurdardottir
I
I
Molnár
V
V
Hammarlund-Udenaes
M
M
Rane
A
A
D000328:Adult; D000368:Aged; D016058:Analgesia, Patient-Controlled / Q000379:methods*; D003061:Codeine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003915:Dextromethorphan / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010149:Postoperative Pain / Q000188:drug therapy*; D010641:Phenotype
D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D003061:Codeine