Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability

Title

Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability

Creator

Williams DG; Patel A; Howard RF

Publisher

British Journal Of Anaesthesia

Date

2002

Subject

Child; Female; Male; Analgesics; Double-Blind Method; Phenotype; Urban Population; Preschool; Non-U.S. Gov't; Anti-Inflammatory Agents; Human; Support; Vomiting/chemically induced; Genotype; Analgesia; Tonsillectomy; Non-Steroidal/administration & dosage; Morphine Derivatives/blood; Central Nervous System Stimulants/blood; Codeine/genetics/metabolism; Diclofenac/administration & dosage; Morphine/metabolism; Opioid/metabolism

Description

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.
2002

Rights

Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).

Type

Journal Article

Citation List Month

Backlog

Pages

839-45

Issue

6

Volume

89

Citation

Williams DG; Patel A; Howard RF, “Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability,” Pediatric Palliative Care Library, accessed October 16, 2021, https://pedpalascnetlibrary.omeka.net/items/show/12581.

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