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Codeine

Opioidoral · inferred

Prodrug opioid analgesic that is O-demethylated to morphine by CYP2D6. Analgesic effect depends on CYP2D6 phenotype: poor metabolizers get little benefit, ultrarapid metabolizers risk toxicity. ~10% of dose converted to morphine.

Projected serum levels — 30 mg, as needed (shown daily)

CodeineMorphine
Codeine modeled serum levels, 30 mg as needed (shown daily) over 15 days Population-based pharmacokinetic estimate. Steady state reached after approximately 1 days. 0 6.3 12.5 18.8 25 Day 0 Day 4 Day 8 Day 11 Day 15 Time on a regular schedule ≈ steady state · day 1

Maintenance schedule: 30 mg as needed (shown daily) (oral).

Modeled steady state after ~1 days: peak ≈ 21.3 mg, trough ≈ 0.12 mg body load. Population-based estimate over 15 days for a 30 mg dose at a 70 kg reference body mass — the interactive app scales curves to your doses, timing, and body mass.

Key facts

Category
Opioid
Route modeled
Oral
Model confidence
inferred
Half-life
3 h
Common dose
30 mg
Suggested maximum
240 mg/day
Reference dose range
15–240 mg (single dose)
Suggested cadence
as needed (shown daily)
Validated against
60 mg oral — Cmax 0.14 mg/L at 1 h

Documented interactions

  • danger
    1,4-BDO (1,4-Butanediol) + Codeine Contraindicated

    1,4-BDO converts to GHB. Codeine metabolizes to morphine. Stacked CNS depression is dangerous.

  • danger
    7-Hydroxymitragynine (7-OH) + Codeine Contraindicated

    7-Hydroxymitragynine is a potent mu-opioid agonist. Codeine is metabolized to morphine. Combined mu-agonism creates additive respiratory depression risk.

  • danger
    CBD (Cannabidiol) + Codeine CYP inhibition

    CBD (Cannabidiol) reversible_inhibitor of UGT2B7 predicted to change Codeine AUC by ~2.11x

  • danger
    Cocaine + Codeine Contraindicated

    Stimulant + opioid combination: cocaine masks sedation, increasing overdose risk.

  • danger
    Ethanol (Alcohol) + Codeine Contraindicated

    Alcohol potentiates opioid respiratory depression. Codeine is metabolized to morphine; alcohol increases CNS depression.

  • danger
    Gabapentin (Neurontin) + Codeine Potentiation

    Gabapentin + opioids significantly increases respiratory depression risk. FDA black box warning.

Serum checks 72 modeled interaction pairings for codeine across your whole stack — absorption conflicts, enzyme inhibition, and nutrient depletion included.

Research behind this entry

  1. Pharmacokinetics of Codeine and Its Metabolite Morphine in Ultra-Rapid Metabolizers due to CYP2D6 Duplication Kirchheiner J et al. · The Pharmacogenomics Journal, 2007 DOI

    Measured codeine and morphine pharmacokinetics over 24 h in CYP2D6 ultra-rapid metabolizers, showing significantly higher morphine exposure due to gene duplication.

  2. Codeine Intoxication Associated with Ultrarapid CYP2D6 Metabolism Gasche Y et al. · New England Journal of Medicine, 2004 DOI

    Case report and pharmacogenetic analysis showing life-threatening opioid intoxication from codeine in a CYP2D6 ultrarapid metabolizer due to excessive morphine formation.

  3. Codeine and Morphine in Extensive and Poor Metabolizers of Sparteine: Pharmacokinetics, Analgesic Effect and Side Effects Poulsen L et al. · European Journal of Clinical Pharmacology, 1996 DOI

    Compared codeine-to-morphine conversion in CYP2D6 extensive vs poor metabolizers, demonstrating that poor metabolizers produce negligible morphine and have reduced analgesia.

3 published studies referenced in the app, each with a plain-language summary.