British Journal of Anaesthesia, 2002, Vol. 89, No. 6 839-845
© 2002 The Board of Management and Trustees of the British Journal of Anaesthesia
Clinical Investigations |
Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability
1 Anaesthetic Department, The Royal London Hospital, Whitechapel, London E1 1BB, UK. 2 Portex Department of Anaesthesia, Institute of Child Health, Guilford Street, London WC1N 1EH, UK. 3 Anaesthetic Department, The Royal National Throat, Nose and Ear Hospital, Grays Inn Road, London WC1X 8DA, UK. 4 Department of Anaesthesia, Great Ormond Street Hospital for Children NHS Trust and Children Nationwide Pain Research Centre, Great Ormond Street, London WC1N 3JN, UK r.howard@ich.ucl.ac.uk
Background. Codeine analgesia is wholly or mostly due to its metabolism to morphine by the cytochrome P450 enzyme CYP2D6, which shows significant genetic variation in activity. The aims of this study were to investigate genotype, phenotype and morphine production from codeine in children undergoing adenotonsillectomy, and to compare analgesia from codeine or morphine combined with diclofenac.
Methods. Ninety-six children received either codeine 1.5 mg kg–1 or morphine 0.15 mg kg–1 in a randomized, double-blind design. Genetic analysis was performed and plasma morphine concentrations at 1 h were determined. Postoperative analgesia and side-effects were recorded.
Results. Forty-seven per cent of children had genotypes associated with reduced enzyme activity. Mean (SD) morphine concentrations were significantly lower (P<0.001) after codeine [4.5 (0.3) ng ml–1] than after morphine [24.7 (1.5) ng ml–1], and morphine and its metabolites were not detected in 36% of children given codeine. There was a significant relationship between phenotype and plasma morphine (P=0.02). More children required rescue analgesia after codeine at both 2 (P<0.05) and 4 h after administration (P<0.01). Fifty-six per cent of children vomited after morphine and 29% after codeine (P<0.01). Neither phenotype nor morphine concentration was correlated with either pain score or the need for rescue analgesia (r=–0.21, 95% confidence interval –0.4, –0.01).
Conclusions. Reduced ability for codeine metabolism may be more common than previously reported. Plasma morphine concentration 1 h after codeine is very low, and related to phenotype. Codeine analgesia is less reliable than morphine, but was not well correlated with either phenotype or plasma morphine in this study.
Br J Anaesth 2002; 89: 839–45
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