How long does codeine stay in system
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Duration of Codeine in the System
Codeine Half-Life and Pharmacokinetics
Codeine Half-Life: The half-life of codeine, which is the time it takes for the concentration of the drug in the bloodstream to reduce by half, is approximately 2.9 hours when administered as a simple aqueous solution1. This short half-life necessitates frequent dosing, typically every 4 hours, to maintain its therapeutic effect.
Controlled Release Formulations: Advances in drug formulations have led to the development of controlled release versions of codeine. For instance, a novel liquid controlled release formulation of codeine has been shown to extend the half-life to about 8.2 hours, allowing for administration every 12 hours while maintaining equivalent bioavailability1. This extended release formulation helps in reducing the frequency of dosing and potentially improves patient compliance.
Excretion of Codeine and Metabolites
Urinary Excretion: Codeine is primarily excreted through urine. Studies in dogs have shown that 4 to 11 percent of the administered codeine is excreted as free codeine, while 42 to 58 percent is excreted as conjugated codeine2. In monkeys, the urinary recovery of codeine is slightly different, with 3 to 10 percent excreted as free codeine and 27 to 39 percent as conjugated codeine2.
Fecal and Biliary Excretion: Fecal excretion of codeine is minimal, accounting for only 0.8 to 1.5 percent of the administered dose in dogs, and is similarly insignificant in monkeys2. Biliary excretion of both free and conjugated codeine is negligible in dogs2.
Conclusion
In summary, the half-life of codeine in the human body is approximately 2.9 hours, necessitating frequent dosing. However, controlled release formulations can extend this half-life to about 8.2 hours, reducing the frequency of administration. Codeine is primarily excreted through urine, with minimal excretion through feces and bile. Understanding these pharmacokinetic properties is crucial for optimizing therapeutic regimens and improving patient outcomes.
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Most relevant research papers on this topic
Pharmacokinetics of a novel liquid controlled release codeine formulation
The novel liquid controlled release codeine formulation, containing a non-coated codeine:ion exchange resin complex, shows improved bioavailability and longer half-life compared to the older Codipertussin® formulation.
RCTPlasma levels and excretion of codeine and metabolites in the dog and monkey.
Codeine has a short half-life in dogs and a long half-life in monkeys, with urinary recovery accounting for most of the drug's excretion.
Non-RCT
Animal StudyEffect of codeine on CYP450 isoform activity of rats
Continuous 14-day intragastric administration of codeine may inhibit the metabolism of bupropion (CYP2B1) and midazolam (CYP3A2) in rats, potentially causing liver damage.
RCTAnimal StudyComparative disposition of codeine and pholcodine in man after single oral doses.
Codeine is rapidly absorbed and eliminated, while pholcodine undergoes little conjugation and is not detectable in plasma after administration.
Non-RCTAntemortem conversion of codeine to morphine in man.
Codeine is partially converted to morphine in the antemortem stage, with more active demethylation in the hepatic system than in blood and other tissues studied.
In Vitro StudyUrine and plasma pharmacokinetics of codeine in healthy volunteers: implications for drugs-of-abuse testing.
The relative proportion of codeine and morphine varies between individuals and over time, with morphine often present in higher concentrations than codeine even after moderate and single doses of codeine.
RCTSingle dose oral codeine, as a single agent, for acute postoperative pain in adults.
Single dose codeine 60 mg provides good analgesia to few individuals and does not compare favorably with commonly used alternatives like paracetamol, NSAIDs, and their combinations with codeine.
Meta-Analysis
Very Rigorous JournalPharmacokinetics and pharmacodynamics of codeine in end‐stage renal disease
Codeine elimination half-life and mean residence time are significantly increased in patients on chronic hemodialysis, suggesting a need for dosage adjustment in these patients.
Non-RCT
Highly CitedAppraisal of Codeine as an Analgesic in Older Patients *
Codeine showed no significant pain relief advantage over placebo in elderly cancer patients, and may have constipating effects.
RCTEfficacy of controlled-release codeine in chronic non-malignant pain: a randomized, placebo-controlled clinical trial
Controlled-release codeine significantly reduces pain and pain-related disability in patients with chronic non-malignant pain, with long-term results similar to those in the double-blind study.
RCTHighly Cited