Analgesic effect and plasma concentrations of codeine and morphine after two dose levels of codeine following oral surgery

  title={Analgesic effect and plasma concentrations of codeine and morphine after two dose levels of codeine following oral surgery},
  author={Hans Quiding and G Lundqvist and Lars O. Bor{\'e}us and U. G. Bondesson and John {\"O}hrvik},
  journal={European Journal of Clinical Pharmacology},
SummaryA double blind randomised cross over investigation was carried out in 25 male patients undergoing two oral surgical extractions, one for each lower wisdom tooth. The two extractions were performed about 6 weeks apart and were carried out under local anaesthesia. One hour after each extraction the patients randomly received 90 or 45 mg codeine. During the following 5 h the patients rated the intensity of their pain on a visual analogue scale. Blood was simultaneously sampled and assayed… 

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

Codeine analgesia is less reliable than morphine, but was not well correlated with either phenotype or plasma morphine in this study, suggesting reduced ability for codeine metabolism may be more common than previously reported.

Codeine and clinical impairment in samples in which morphine is not detected

Codeine appeared to have some dose-dependent effect on the central nervous system that may lead to impairment as judged from a CTD, independent of measurable blood morphine concentrations, which supports the view that some codeine effects do not seem to be mediated by morphine.

A review of the efficacy and safety of opioid analgesics post-craniotomy.

It is argued, in this paper, that codeine phosphate is an unpredictable pro-drug that does not equate to a safe and effective method of providing analgesia post-craniotomy, and there is an explicit challenge to the neurosurgical community to re-evaluate their pain-management strategies.

Codeine to morphine concentration ratios in samples from living subjects and autopsy cases after incubation.

If codeine and morphine glucuronides are subject to cleavage to the same extent in living and autopsy cases in vitro is investigated and a reduction in the codeine to morphine concentration ratio was found.

Role of active metabolites in the use of opioids

Clinicians need to be aware that many opioids have active metabolites that will become therapeutically important, for example in cases of altered pathology, drug interactions and genetic polymorphisms of drug-metabolizing enzymes.

Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II.

Understanding of this metabolism of codeine, dihydrocodeine, hydrocodone, oxycodone, and buprenorphine is important so that clinicians can choose the proper dosages for analgesia and anticipate potential drug-drug interactions.

Proceedings of the Symposium "Updates of the Clinical Pharmacology of Opioids with Special Attention to Long-Acting Drugs"

The evidence suggests that the metabolites of several opioids account for an important part of the clinical effects that must be considered in clinical practice.

Genetic Predictors of the Clinical Response to Opioid Analgesics

This review uses a candidate gene approach to identify possible pharmacogenetic modulators of opioid therapy, and discusses these modulators together with demonstrated genetic causes for the

Post‐craniotomy analgesia: current practices in British neurosurgical centres ‐ a survey of post‐craniotomy analgesic practices

  • G. Roberts
  • Medicine
    European journal of anaesthesiology
  • 2005
It is proposed that patient controlled analgesia with morphine is an efficacious and safe alternative to codeine phosphate in post‐craniotomy analgesia.



Plasma codeine and morphine concentrations after therapeutic oral doses of codeine‐containing analgesics

The hypothesis that metabolically produced morphine may influence or be responsible for the analgesic efficacy of codeine is supported.

Plasma Codeine and Morphine Concentrations After a Single Oral Dose of Codeine Phosphate

Plasma concentrations of codeine and its O‐demethylated metabolite morphine were determined, by a sensitive and specific high performance liquid chromatography (HPLC) method, following a single oral

Plasma concentrations of codeine and its metabolite, morphine, after single and repeated oral administration

It seems unlikely that morphine plays a significant role in the analgesic efficacy of single or repeated doses of codeine, as the plasma concentration of morphine was only 2–3% of that ofcodeine during steady-state.

The effect of quinidine on the analgesic effect of codeine

SummaryWe have studied the hypoalgesic effect of codeine (100 mg) after blocking the hepatic O-demethylation of codeine to morphine via the sparteine oxygenase (CYP2D6) by quinidine (200 mg). The

The postoperative pharmacokinetics of codeine

The metabolism and systemic availability of codeine have been studied in 12 patients after cholecystectomy and the formation of morphine from codeine was very small and plasma morphine concentrations were below the detection limit.

Patient-controlled Analgesic Therapy, Part IV: Pharmacokinetics and Analgesic Plasma Concentrations of Morphine

The influence of anaesthesia and surgery on the pharmacokinetics of morphine was studied in 10 patients, and postoperative pain was relieved by patient-controlled administration of intravenous doses of morphine by means of a programmable drug injector.

Infants and young children metabolise codeine to morphine. A study after single and repeated rectal administration.

It is concluded that at the age of 6 months infants are capable of O-demethylating codeine to morphine, suggesting impaired glucuronidation of morphine in the former group.

Codeine disposition in smokers and nonsmokers

The observation of higher morphine AUC values after oral codeine, coupled with clinical reports of greater analgesic potency with intramuscular codeines, does not support the hypothesis that the analgesic properties of this drug are mediated entirely by biotransformation to morphine.