Possible Interaction: Chlorzoxazone and Quercetin

“Consequently, the metabolic ratios of diclofenac and chlorzoxazone were significantly affected by quercetin when compared with previous herb-drug interaction studies [7].”

“Hence, it can be concluded that metabolism of diclofenac and chlorzoxazone was substantially reduced upon quercetin treatment.”

“Hence, it is reasonable to suggest that quercetin has an inhibitory effect on the disposition of chlorzoxazone in healthy subjects.”

“So, it can be expected that enhanced exposure of chlorzoxazone could partly be attributed to inhibition of Pgp and BCRP mediated efflux transport by quercetin.”

“The published study results suggest that treatment with quercetin 500 mg twice daily for 10 days significantly enhanced the exposure of chlorzoxazone , a CYP2E1 substrate, in healthy subjects [1].”

“Therefore, the role of other CYP450 enzymes in the interaction between quercetin and chlorzoxazone may be minor when compared to that of CYP2E1 and the increase in chlorzoxazone exposure by quercetin would be in part due to inhibition of CYP2E1 enzyme activity in the liver.”

“To our knowledge, there are no reports investigating whether chlorzoxazone is a substrate of such efflux transporters; nevertheless, it cannot be ruled out that the enhanced AUC of chlorzoxazone could partly be attributed to the inhibition of efflux transport by quercetin.”

“To the Editor We read a recent publication by Bedada and Neerati on … Journal of Clinical Pharmacology with great interest, reporting the plasma concentrations of chlorzoxazone , an in vivo CYP2E1 probe drug, being significantly increased after 10-days treatment of quercetin (500 mg twice daily) in healthy subjects [1].”

“In addition, geometric mean ratios and 90% confidence intervals for Cmax and AUC of CHZ and 6-OHCHZ were both out of the no-effect boundaries of 0.80–1.25, which indicates a significant pharmacokinetic interaction present between CHZ and quercetin.”

“The blood samples were collected at predetermined time … CHZ and 6-hydroxychlorzoxazone (6-OHCHZ).ResultsTreatment with quercetin significantly enhanced the maximum plasma concentration (Cmax), area under the curve (AUC), and half-life (…, while significantly decreased the elimination rate constant (kel) and apparent oral clearance (CL/F) of CHZ by ….”