Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers.

Chen, ZR; Somogyi, A.; Reynolds, Geoffrey D.; Bochner, Felix

doi:10.1111/j.1365-2125.1991.tb05550.x

Cited by 116 publications

(53 citation statements)

References 37 publications

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“…The safety issue is that some children have duplicated cytochromes that allow greater than expected conversion of the prodrug codeine to morphine, thus resulting in potential overdose; codeine should be avoided for postprocedure analgesia. [320][321][322][323][324] The health evaluation should include the following:…”

Section: Documentation At the Time Of Sedationmentioning

confidence: 99%

Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures: Update 2016

Coté¹,

Wilson²

2016

Pediatrics

254

199

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The safe sedation of children for procedures requires a systematic approach that includes the following: no administration of sedating medication without the safety net of medical/dental supervision, careful presedation evaluation for underlying medical or surgical conditions that would place the child at increased risk from sedating medications, appropriate fasting for elective procedures and a balance between the depth of sedation and risk for those who are unable to fast because of the urgent nature of the procedure, a focused airway examination for large (kissing) tonsils or anatomic airway abnormalities that might increase the potential for airway obstruction, a clear understanding of the medication's pharmacokinetic and pharmacodynamic effects and drug interactions, appropriate training and skills in airway management to allow rescue of the patient, age-and size-appropriate equipment for airway management and venous access, appropriate medications and reversal agents, suffi cient numbers of staff to both carry out the procedure and monitor the patient, appropriate physiologic monitoring during and after the procedure, a properly equipped and staffed recovery area, recovery to the presedation level of consciousness before discharge from medical/dental supervision, and appropriate discharge instructions. This report was developed through a collaborative effort of the

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Section: Documentation At the Time Of Sedationmentioning

confidence: 99%

Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures: Update 2016

Coté¹,

Wilson²

2016

Pediatrics

254

199

View full text Add to dashboard Cite

show abstract

“…This is related to the fact that O-demethylation of codeine to morphine is dependent on cytochrome P450 isoenzyme 2D6, which is known to exhibit genetic polymorphism. Thus, some individuals produce little or no morphine from codeine and others produce significant amounts, although the amount produced may show wide variation (156)(157)(158). Thus, for individuals with moderate to severe pain, a stronger opioid (such as morphine or oxycodone) should be chosen in the first instance, and codeine is not recommended.…”

Section: Conventional Opioidsmentioning

confidence: 99%

The Pharmacotherapy of Chronic Pain: A Review

Lynch

Watson

2006

Pain Research and Management

103

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The past two decades have contributed a large body of preclinical work that has assisted in our understanding of the underlying pathophysiological mechanisms that cause chronic pain. In this context, it has been recognized that effective treatment of pain is a priority and that treatment often involves the use of one or a combination of agents with analgesic action. The current review presents an evidence-based approach to the pharmacotherapy of chronic pain. Medline searches were done for all agents used as conventional treatment in chronic pain. Published papers up to June 2005 were included. The search strategy included randomized, controlled trials, and where available, systematic reviews and meta-analyses. Further references were found in reference sections of papers located using the above search strategy. Agents for which there were no controlled trials supporting efficacy in treatment of chronic pain were not included in the present review, except in cases where preclinical science was compelling, or where initial human work has been positive and where it was thought the reader would be interested in the scientific evidence to date.Key Words: Anticonvulsants; Antidepressants; Cannabinoids; Chronic pain; Opioids; Pharmacotherapy; Topical analgesics La pharmacothérapie de la douleur chronique : Une analyse Les deux dernières décennies ont contribué à un vaste ensemble de travaux précliniques qui nous ont permis de mieux comprendre les mécanismes physiopathologiques sous-jacents responsables de la douleur chronique. Dans ce contexte, il est admis que le traitement efficace de la douleur est une priorité et qu'il exige souvent le recours à un agent ou à une association d'agents ayant une action analgésique. La présente analyse présente une démarche probante de la pharmacothérapie de la douleur chronique. Des recherches dans Medline ont été effectuées sur tous les agents utilisés pour le traitement classique de la douleur chronique. Les articles publiés jusqu'en juin 2005 ont été inclus. La stratégie de recherche incluait les essais aléatoires et contrôlés et, si elles étaient disponibles, les analyses systématiques et les méta-analyses. D'autres références ont été obtenues dans la partie des références des articles trouvés à l'aide de la stratégie de recherche précédente. Les agents dont aucun essai contrôlé n'étayait l'efficacité pour le traitement de la douleur chronique étaient exclus de la présente analyse, sauf si les données scientifiques précliniques étaient convaincantes, si les travaux humains initiaux étaient positifs ou si on pensait que les données scientifiques colligées jusque-là étaient intéressantes pour le lecteur.

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“…It is generally accepted that COD analgesia arises from CYP2D6 catalyzed O-demethylation to form morphine (Somogyi et al, 2007). Approximately 4 to 10% of a COD dose is converted to morphine in CYP2D6-extensive metabolizers (Chen et al, 1991;Yue et al, 1991). Other elimination pathways include glucuronidation, N-demethylation, and renal clearance of unchanged drug.…”

Section: Introductionmentioning

confidence: 99%

In Vitro–In Vivo Extrapolation Predicts Drug–Drug Interactions Arising from Inhibition of Codeine Glucuronidation by Dextropropoxyphene, Fluconazole, Ketoconazole, and Methadone in Humans

Raungrut¹,

Uchaipichat²,

Elliot³

et al. 2010

J Pharmacol Exp Ther

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Because codeine (COD) is eliminated primarily via glucuronidation, factors that alter COD glucuronide formation potentially affect the proportion of the dose converted to the pharmacologically active metabolite morphine. Thus, in vitro-in vivo extrapolation approaches were used to identify potential drug-drug interactions arising from inhibition of COD glucuronidation in humans. Initial studies characterized the kinetics of COD-6-glucuronide (C6G) formation by human liver microsomes (HLM) and demonstrated an 88% reduction in the Michaelis constant (K m ) (0.29 versus 2.32 mM) for incubations performed in the presence of 2% bovine serum albumin (BSA). Of 13 recombinant UDP-glucuronosyltransferase (UGT) enzymes screened for COD glucuronidation activity, only UGT2B4 and UGT2B7 exhibited activity. The respective S 50 values (0.32 and 0.27 mM) generated in the presence of BSA were comparable with the mean K m observed in HLM. Known inhibitors of UGT2B7 activity in vitro or in vivo and drugs marketed as compound formulations with COD were investigated for inhibition of C6G formation by HLM. Inhibition screening identified potential interactions with dextropropoxyphene, fluconazole, ketoconazole, and methadone. Inhibitor constant values generated for dextropropoxyphene (3.5 M), fluconazole (202 M), ketoconazole (0.66 M), and methadone (0.32 M) predicted 1.60-to 3.66-fold increases in the area under the drug plasma concentration-time curve ratio for COD in vivo. Whereas fluconazole and ketoconazole inhibited UGT2B4-and UGT2B7-catalyzed COD glucuronidation to a similar extent, inhibition by dextropropoxyphene and methadone resulted largely from an effect on UGT2B4. Interactions with dextropropoxyphene, fluconazole, ketoconazole, and methadone potentially affect the intensity and duration of COD analgesia.The opioid codeine (COD) is one of the most widely used drugs worldwide. COD is used extensively in the treatment of mild to moderate pain, either alone or in combination with other analgesics. Furthermore, COD is used as an antitussive and for the treatment of diarrhea. It is generally accepted that COD analgesia arises from CYP2D6 catalyzed O-demethylation to form morphine (Somogyi et al., 2007). Approximately 4 to 10% of a COD dose is converted to morphine in CYP2D6-extensive metabolizers (Chen et al., 1991;Yue et al., 1991). Other elimination pathways include glucuronidation, N-demethylation, and renal clearance of unchanged drug. Of these, glucuronidation, to form COD-6-glucuronide (C6G), is the dominant metabolic pathway, accounting for 80 to 85% of the COD dose recovered in urine (Yue et al., 1991).Accumulating evidence indicates that the relative formation of morphine plays a pivotal role in COD response. In

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Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers.

Cited by 116 publications

References 37 publications

Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures: Update 2016

Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures: Update 2016

The Pharmacotherapy of Chronic Pain: A Review

In Vitro–In Vivo Extrapolation Predicts Drug–Drug Interactions Arising from Inhibition of Codeine Glucuronidation by Dextropropoxyphene, Fluconazole, Ketoconazole, and Methadone in Humans

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