Pharmacokinetic interactions induced by content variation of major water-soluble components of Danshen preparation in rats

Abstract

Aim: To investigate the pharmacokinetic interactions induced by content variation of the main water-soluble components of Danshen injection in rats. Methods: Intravenous Danshen injection (control) or Danshen injection with danshensu (DSS), protocatechuic aldehyde (PAL), salvianolic acid A (Sal A) or salvianolic acid B (Sal B) were administered to female Sprague Dawley rats . Plasma concentrations of DSS, Sal A, PAL and its oxidative metabolite protocatechuic acid (PA) were analyzed simultaneously with LC-MS/MS; concentrations of Sal B were determined by the LC-MS method. Non-compartmental pharmacokinetic parameters were calculated and compared for identifying the pharmacokinetic interactions among these components. Results: Compared with the control group, the DSS, Sal A, and Sal B groups had significant increases in AUC 0-∞ in response to elevated concentrations of PAL ( by 78.1%, 51.0%, and 82.9%, respectively), while the clearances (CL) were markedly reduced (by 42.5%, 32.9%, and 46.8%, respectively). Similarly, Sal A increased the AUC 0-∞ of DSS and Sal B (26.7% and 82.4%, respectively) and substantially decreased their clearances (21.4% and 45.6%, respectively). In addition, the pharmacokinetics of DSS and Sal B were significantly affected by the content variation of the other major components; the AUC 0-∞ increased by 45.1% and 52.1%, respectively, the CL dropped by 29.6% and 27.1%, respectively, and the T 1/2 was decreased by 22.0% and 19.6%, respectively. Conclusion: Complex, extensive pharmacokinetic interactions were observed among the major water-soluble constituents in the Danshen injection. The content variation of PAL had the most significant effect on the pharmacokinetic behaviors of other major constituents. Furthermore, the pharmacokinetics of DSS and Sal B were the most susceptible to the content change of other components.

HPLC and LC-MS analysis of sinomenine and its application in pharmacokinetic studies in rats

“…Chloramphenicol (internal standard) was obtained from Baijingyu Pharma (purity: 99.98%, Nanjing, China) [12] . HPLC-grade methanol was purchased from Merck & Co, Inc (Germany).…”

Some pharmacokinetic parameters of salvianolic acid A following single-dose oral administration to rats

“…Drug interactions tend to exist when drugs are used in combination, and pharmacokinetic interactions were observed among the components of Salvia miltiorrhiza extract (Chang et al. 2010 ). Based on the above studies, some questions were raised.…”

Identification of multiple components in Guanxinning injection using hydrophilic interaction liquid chromatography/time‐of‐flight mass spectrometry and reversed‐phase liquid chromatography/time‐of‐flight mass spectrometry

“…The major components of GXNI are saccharides, organic acids, amino acids, phenolic acids and phthalides. Recently, some active ingredients in its crude drugs related to these pharmacological functions have been identified . With a few exceptions, studies on quality control methods of GXNI are scarce due to the complexity of the preparation and the lack of authentic standards.…”

“…Recently, some active ingredients in its crude drugs related to these pharmacological functions have been identified. [3][4][5][6][7][8] With a few exceptions, studies on quality control methods of GXNI are scarce due to the complexity of the preparation and the lack of authentic standards. Cao et al developed a reversed-phase liquid chromatography ultraviolet (RPLC-UV) method for determination of danshensu and protocatechuic aldehyde in GXNIs.…”