The rhubarb total free anthraquinone oral colon-specific drug delivery granules: Comparative pharmacokinetics study with rhubarb by UPLC-MS/MS after oral administration

Abstract

ObjectiveThis study aimed to compare pharmacokinetics of rhubarb total free anthraquinones (AQs) oral colon-specific delivery granules (RTFA-OCDD-GN) and rhubarb after oral administration to evaluate the colonic-target releasing characteristic of RTFA-OCDD-GN and the impact of five AQs components on the contribution of the attenuation of nephrotoxicity. MethodsThe compare pharmacokinetics of RTFA-OCDD-GN and rhubarb was performed in rats. The plasma concentrations of aloe-emodin, rhein, emodin, chrysophanol and physcion were assayed by a validated UPLC-MS/MS method. ResultsThe pharmacokinetics results showed that the AUC0-72h of aloe-emodin, emodin, chrysophanol and physcion was decreased by 3.09-fold (p < 0.05), 2.68-fold (p < 0.05), 2.97-fold (p < 0.01) and 2.84-fold (p < 0.05) respectively in group RTFA-OCDD-GN; whereas the AUC0-72h of rhein was increased slightly by 1.05-fold (p > 0.05) compared with group rhubarb samples. However the dose-normalized AUC0-72h of aloe-emodin, rhein, emodin and chrysophanol was decreased by 1.90-fold (p < 0.05), 1.82-fold, 1.33-fold and 2.27-fold (p < 0.01) respectively in RTFA-OCDD-GN group; whereas the dose-normalized AUC0-72h of physcion was increased by 2.33-fold (p < 0.01) compared with group rhubarb samples. ConclusionThese differences on pharmacokinetic parameters indicated that RTFA-OCDD-GN delivered AQs to colon. The systemic exposure reduction of aloe-emodin, emodin and physcion in group RTFA-OCDD-GN could contribute to the attenuation of nephyrotoxicity caused by rhubarb.