Effects of diclofenac on the pharmacokinetics of celastrol in rats and its transport

Context: Diclofenac and celastrol are always used together for the treatment of rheumatoid arthritis; the herb–drug interaction potential between diclofenac and celastrol is still unknown.

Objective: This study investigates the effects of diclofenac on the pharmacokinetics of celastrol in rats.

Materials and methods: Twelve male Sprague-Dawley rats were divided into two groups and received celastrol (1?mg/kg) or both celastrol (1?mg/kg) and diclofenac (10?mg/kg) by oral gavage, and blood samples were collected via the oculi chorioideae vein and determined using the LC-MS method developed in this study. Additionally, the effects of diclofenac on the transport of celastrol were investigated using a Caco-2 cell transwell model.

Results: Diclofenac could significantly (p?C_max (from 66.93?±?10.28 to 41.25?±?8.06?ng/mL) and AUC_0-t (from 765.84?±?163.61 to 451.33?±?110.88?μg?×?h/L) of celastrol in rats. The efflux ratio of celastrol increased significantly (p?Discussion and conclusion: These results indicated that diclofenac could decrease the system exposure of celastrol in rats when they are co-administered, and these effects might be exerted via decreasing its absorption in intestine.