Pharmacokinetics comparison of four major bio-active components in normal and blood stasis rats after administration of Naoxintong Capsule by UPLC-TQ/MS

Abstract

Background Blood stasis is one major cause of cardiovascular and cerebrovascular diseases. Naoxintong capsule (NXTC), a Chinese patent medicine, has been widely employed in the prevention and treatment against cardiovascular and cerebrovascular diseases. However, the pharmacokinetics comparison of NXTC in normal and blood stasis rats were remain obscured. Methods Acute blood stasis rats were induced by being placed in ice-cold water during the interval between two injections of adrenaline hydrochloride. Normal and blood stasis rats were administrated of NXTC suspension at the dosage of 5 g⋅kg -1 , and blood was collected at different time points after then. Concentrations of four main components including caffeic acid, ferulic acid, formononetin and tanshinone IIA in rat plasma were quantified by UPLC-TQ/MS. The pharmacokinetic parameters were calculated by Phoenix WinNonlin v6.2 software. Results It was found that C max , AUC all , AUC INF_obs , Vz_F_obs and MRT last of ferulic acid, AUC all, Vz_F_obs and MRT last of caffeic acid in blood stasis rats were significantly different ( P < 0.05) from normal rats. Compared with normal rats, C max of ferulic acid and formononetin decreased significantly in the plasma of acute blood stasis rats, AUC all of caffeic acid and ferulic acid decreased notably, AUC INF_obs of ferulic acid decreased remarkably, Vz_F_obs and MRT last of ferulic acid and caffeic acid increased reversely. It is suggested that the absorption of the four components of NXTC in acute blood stasis rats was weakened, and the elimination time was prolonged. Conclusions The significant difference in some different parameters of the 4 NXTC components in normal and blood stasis rats might be caused by increasing of blood viscosity and slowing down of blood flow in acute blood stasis rats. The pharmacokinetic study under pathological condition provided important information for more rational use of NXTC in clinical situations.