Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine are governed by CYP2D6 activity. Polymorphisms are a major cause of CYP2D6 variability. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for codeine based on CYP2D6 genotype. This documen...

Delta9-tetrahydrocannabinol (delta9-THC) synergizes with morphine and codeine by releasing endogenous opioids. These studies determined 1) the duration of enhancement of morphine and codeine by delta9-THC, 2) the effect of (delta9-THC on the time course of fully efficacious doses of the opioids, 3) restoration of efficacy of morphine and codeine by delta9-THC, and 4) duration of restoration. Su...

BACKGROUND Both the Department of Defense (DoD) and the Department of Health and Human Services (DHHS) currently require two confirmation tests to verify use of heroin, one test for total morphine and a separate test for 6-acetylmorphine (6-AM). Our aim was to determine appropriate free-codeine, free-morphine, and 6-AM cutoff concentrations that could be substituted for total-morphine, total-co...

QUESTION Recently a newborn died from morphine poisoning when his mother used codeine while breastfeeding. Many patients receive codeine for postlabour pain. Is it safe to prescribe codeine for nursing mothers? ANSWER When a mother is an ultrarapid metabolizer of cytochrome P450 2D6, she produces much more morphine when taking codeine than most people do. In this situation, newborns might be ...

Codeine is metabolized by glucuronidation, by O-demethylation to morphine, and by N-demethylation to norcodeine. The enzyme responsible for the O-demethylation to morphine has been identified as cytochrome P4502D6 (CYP2D6). The purpose of the present study was to identify the specific P450 enzyme responsible for codeine N-demethylation. Microsomal preparations (250 pmol of P450) obtained from 1...

BACKGROUND Misuse of prescription and over-the-counter codeine-containing products is a global public health issue. OBJECTIVES To investigate the extent of treatment demand related to the misuse of codeine or codeine dependence in South Africa (SA) and the profile of patients seeking treatment, so as to understand the nature and extent of the problem. METHOD Data were collected from centres...

A gas-chromatographic method is described for determination of codeine and norcodeine in human plasma. The method is specific, sensitive, and precise. It was developed for use in bioavailability studies of therapeutic doses of codeine sulfate. After ingestion of a 60-mg codeine sulfate tablet, mean peak codeine concentration in plasma was 107 mug/liter at 1.0 hour. No measurable concentration o...

BACKGROUND Previously, we have demonstrated a marked inhibition of codeine glucuronidation by diclofenac in human liver tissue homogenate. We therefore aimed to investigate whether diclofenac inhibits glucuronidation of codeine also in vivo in healthy volunteers. METHODS In a randomised, placebo-controlled, double-blind, cross-over study, 12 healthy volunteers received a singe of 100 mg codei...

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. ...

BACKGROUND AND OBJECTIVES National guidelines have recommended against codeine use in children, but little is known about prescribing patterns in the United States. Our objectives were to assess changes over time in pediatric codeine prescription rates in emergency departments nationally and to determine factors associated with codeine prescription. METHODS We performed a serial cross-section...