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Last Updated: 2 years ago

Possible Interaction: Diclofenac and Quinidine

supplement:

Quinidine

Research Papers that Mention the Interaction

In incubations with CYP3A4 ‘freed’ from its host membrane, the 5-hydroxylation of diclofenac increased with increasing quinidine concentrations, reaching a maximal eightfold elevation relative to controls.
Xenobiotica; the fate of foreign compounds in biological systems  •  2004  |  View Paper
In this case, enhancement by quinidine of diclofenac metabolism in vitro was attributed to increases in the V(max) with little contribution from changes in the K(m) value.
Nevertheless, the in vivo significance of CYP3A cooperativity was demonstrated in a pharmacokinetic study in monkeys, wherein the hepatic clearance of diclofenac increased 2-fold when quinidine was co-administered.
The 5-hydroxylation of diclofenac is subject to CYP3A4 cooperativity elicited by quinidine.
Current drug metabolism  •  2003  |  View Paper
When diclofenac was incubated with human liver microsomes in the presence of quinidine , the formation of 5-hydroxydiclofenac increased approximately 6-fold relative to controls.
Drug metabolism and disposition: the biological fate of chemicals  •  2000  |  View Paper
RESULTS Concomitant administration of di lofenac re duced the partial clearance of qui nidine by N-oxidation by 27%, while no effect was found for other pharmacokinetic parameters of quinidine.
British journal of clinical pharmacology  •  1999  |  View Paper
The cytochrome P-450 (CYP)3A4-mediated metabolism of diclofenac is stimulated in vitro by quinidine.
Therefore, the decreases in plasma concentrations of diclofenac after a combined dose of diclofenac and quinidine are taken to reflect increased hepatic clearance of the drug, presumably resulting from the stimulation of CYP3A-catalyzed oxidative metabolism.
These data suggest that the catalytic capacity of monkey hepatic CYP3A toward diclofenac metabolism is enhanced by quinidine.
We describe an in vivo interaction of diclofenac and quinidine that leads to enhanced clearance of diclofenac in monkeys.
When diclofenac was coadministered with quinidine (0.25 mg/kg/h) via the same route, the corresponding plasma diclofenac concentrations were 50, 59, and 18 ng/ml, representing 57, 56, and 56% of control values, respectively.
The Journal of pharmacology and experimental therapeutics  •  1999  |  View Paper
…,diclofenac … quinidine resulting in doubling of the potency of this inhibitor i.e. lowering the measured IC(50) of diclofenac from 311 μM down to 157 … employed for in vitro studies of not only drug-drug interactions but also prediction of adverse drug reactions in this important P450 isozyme.
Bioelectrochemistry  •  2012  |  View Paper