Celecoxib is a CYP1A2 inhibitor in vitro but not in vivo

European Journal of Clinical Pharmacology
Marjo J KarjalainenJanne T Backman

Abstract

We recently discovered that rofecoxib is a potent mechanism-based inhibitor of CYP1A2. The effect of the widely used cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drug celecoxib on CYP1A2 activity has not been reported. The effect of celecoxib on CYP1A2 activity (phenacetin O-deethylation) was first studied in vitro using human liver microsomes. This was followed by a randomized, placebo-controlled, cross-over study in which 12 healthy volunteers were given celecoxib (200 mg twice daily) or placebo for 4 days. On day 3, a caffeine test was performed. On day 4, the subjects ingested 2 mg tizanidine. Plasma samples for the measurement of the concentrations of tizanidine, its metabolites and celecoxib were collected up to 24 h post-administration. Pharmacodynamic variables (e.g. blood pressure, subjective drowsiness and drug effect) were recorded up to 12 h post-adm. Celecoxib was found to be a moderately potent competitive inhibitor of CYP1A2 in vitro with a K(i) (inhibitor constant) of 25.4 microM. However, in vivo, celecoxib did not affect the caffeine test, or the peak concentration, time to peak concentration, area under the concentration-time curve or half-life of tizanidine. The pharmacodynamic variables of ti...Continue Reading

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Citations

Nov 30, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jiawang LiuMaryam Foroozesh
Oct 1, 2009·Journal of Clinical Pharmacology·Kenji MomoYukinao Kohda
Feb 2, 2013·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Kenji MomoYukinao Kohda
Jan 6, 2021·Current Drug Metabolism·Jingchao GuoXu Wang
Jul 9, 2009·Current Opinion in Anaesthesiology

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