Diacerein (diacetylrhein) is clinically used for the treatment of osteoarthritis in Europe. Rhein was the assay target of pharmacokinetic study of diacerein after oral administration. Numerous studies have reported that rhein possessed anticancer, antiangiogenesis, hepaprotective and hypoglycemia activities. Therefore, we anticipate that in addition to osteoarthritis treatment, diacerein has the potential to be developed for new indications.
Diacerein is insoluble in water. To enhance the oral bioavailability, solid dispersion of diacerein was prepared by melt method and pharmacokinetic study using rats was employed to develop optimum formulation. After rats were administered orally with 40 mg/kg of diacerein solid disersion, blood samples were withdrawn via cardiopuncture at designated time. A HPLC method was used to determine the concentrations of rhein before and after hydrolysis with β-glucuronidase and sulfatase, respectively. The results showed that rhein glucuronides were predominantly present in the circulation, whereas rhein sulfates and rhein free form were present at lower concentrations.
Methotrexate (MTX) is a bicarboxylate immunosuppressant and anticancer agent with narrow therapeutic window. The transport of MTX was associated with multidrug resistance-associated protein (MRPs) and organic anion transporter (OATs). Folium Sennae (leaves of Cassia angustifolia) was used as a potent laxative. Previous study revealed that after intake of Folium Sennae, the major molecules in blood were rhein glucuronides/sulfates and rhein, which were probable substrates of MRPs and OATs. This study investigated the effect of Folium Sennae decoction (FSD) coadministration on MTX pharmacokinetics in rats. The results showed that single-dose or multiple-dose coadministration of FSD significantly increased the AUC720-2880 and MRT of MTX. Therefore, the risk or benefit of combined therapy using MTX with FSD for clinical use warrants caution and more studies.
