PT  - JOURNAL ARTICLE
AU  - Susanne Ammon
AU  - Oliver von Richter
AU  - Ute Hofmann
AU  - Klaus-Peter Thon
AU  - Michel Eichelbaum
AU  - Gerd Mikus
TI  - In Vitro Interaction of Codeine and Diclofenac
DP  - 2000 Oct 01
TA  - Drug Metabolism and Disposition
PG  - 1149--1152
VI  - 28
IP  - 10
4099  - http://dmd.aspetjournals.org/content/28/10/1149.short
4100  - http://dmd.aspetjournals.org/content/28/10/1149.full
SO  - Drug Metab Dispos2000 Oct 01; 28
AB  - There is very limited knowledge about possible pharmacokinetic interactions between opioid analgesics and nonsteroidal antiinflammatory drugs (NSAIDs), which are commonly used in combination for the treatment of chronic pain. The major metabolic pathway of the weak opioid codeine is glucuronidation to codeine-6-glucuronide. Therefore we investigated the influence of the NSAID diclofenac on the formation of codeine-6-glucuronide in vitro, using human liver tissue homogenate. The formation of codeine-6-glucuronide exhibited single enzyme Michaelis-Menten kinetics with an averageVmax of 93.6 ± 35.3 pmol/mg/min. A noncompetitive inhibition of codeine-6-glucuronidation by diclofenac was observed with an average Ki of 7.9 μM. These in vitro findings suggest that a pharmacokinetic interaction occurs in vivo, which has to be confirmed by an interaction study in human subjects. It can be speculated that in case of inhibition of glucuronidation, the amount of codeine available for other pathways especially O-demethylation to morphine is increased, resulting in higher morphine serum levels and therefore higher analgesic efficacy. The American Society for Pharmacology and Experimental Therapeutics