Wenzheng Ju
Jiangsu Provincial Hospital of Traditional Chinese Medicine, China
Title: Oral bioavailability and gender-related pharmacokinetics of celastrol following administration of pure celastrol and its related tablets in rats
Biography
Biography: Wenzheng Ju
Abstract
Celastrol is a natural compound extracted from the traditional Chinese medicinal herb, Thunder God Vine (TGV). Owing to its potential anti-inflammatory and anti-tumor effects, celastrol has been considered as a promising candidate for drug development. Sprague–Dawley rats were administrated an intravenous dose (100 μg•kg-1) of pure celastrol and an oral dose (1000 μg•kg-1) of pure celastrol and TGV tablets (corresponding to 534 μg•kg-1 of celastrol), respectively. At different time points, the concentration of celastrol in rat plasma was determined by a sensitive and well-validated LC–MS/MS method. Main pharmacokinetic parameters including AUC, Cmax, Tmax and MRT were estimated. The oral absolute bioavailability of celastrol significantly increased from 17.06% for pure celastrol to 94.19% for TGV tablets containing equivalent celastrol. After oral administration of TGV tablets, the Cmax and AUC values of celastrol in female rats were (32.03±8.41) μg•L-1 and (379.49±118.19) μg•h•L-1, which was significantly higher (p<0.01) than that in males with the values of (14.31±7.33) μg•L-1 and (188.17±92.33) μg•h•L-1.Celastrol administered orally in the rat was poorly absorbed into the systemic circulation. However, the poor absorption of celastrol could be greatly improved when celastrol-containing TGV tablets orally administered, and thereby the oral bioavailability of celastrol was significantly increased. As for gender difference, female rats showed significantly better absorption of celastrol than males. Plasma concentration–time profiles of celastrol following (a) intravenous injection and (b) oral administration of pure celastrol standard in female rats, as well as oral administration of TGV tablets in (c) female and (d) male rats.