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In vitro interaction of codeine and diclofenac
S Ammon1, O von Richter, U Hofmann
1Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. susanne.ammon@medizin.uni-magdeburg.de
Drug Metabolism and Disposition: the Biological Fate of Chemicals
|September 21, 2000
Summary
Diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), inhibits codeine metabolism in vitro. This interaction may increase codeine
Area of Science:
- Pharmacology
- Drug Metabolism
- Pain Management
Background:
- Limited knowledge exists on pharmacokinetic interactions between opioid analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs).
- Opioids and NSAIDs are frequently co-prescribed for chronic pain management.
- Codeine, a weak opioid analgesic, is primarily metabolized via glucuronidation to codeine-6-glucuronide.
Purpose of the Study:
- To investigate the in vitro effect of diclofenac on codeine-6-glucuronidation.
- To understand potential pharmacokinetic interactions between codeine and NSAIDs.
Main Methods:
- In vitro study using human liver tissue homogenate.
- Assessed the influence of diclofenac on codeine-6-glucuronide formation.
- Analyzed kinetics using Michaelis-Menten models and determined inhibition constants (Ki).
Main Results:
- Codeine-6-glucuronidation followed single enzyme Michaelis-Menten kinetics (Vmax: 93.6 ± 35.3 pmol/mg/min).
- Diclofenac non-competitively inhibited codeine-6-glucuronidation with a Ki of 7.9 μM.
- In vitro findings suggest a potential in vivo pharmacokinetic interaction.
Conclusions:
- Diclofenac inhibits codeine glucuronidation in vitro.
- This interaction may alter codeine's metabolic profile, potentially increasing morphine levels.
- Further in vivo studies in human subjects are warranted to confirm these findings and their clinical implications for pain management.