Plasma and cerebrospinal fluid pharmacokinetics of hydroxysafflor yellow A in patients with traumatic brain injury after intravenous administration of Xuebijing using LC-MS/MS method

Abstract

1. Hydroxysafflor yellow A (HSYA) is the most pharmaceutically relevant compound in Xuebijing (XBJ) for traumatic brain injury (TBI) treatment. We aimed to investigate biofluids pharmacokinetics of HSYA from XBJ to ensure the drug safety and to guide the clinical use.

2. A sensitive, rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was applied to investigate pharmacokinetics of HSYA in TBI patients after intravenous administration of XBJ. Non-compartmental methods using DAS 3.0 software were applied to analyse the pharmacokinetic parameters.

3. A similar half-life (Plasma_t1/2: 14.55 ± 3.51 h vs. CSF_t1/2: 15.73 ± 3.63) was observed. HSYA reached the peak level rapidly, but exhibited a strongly slow absorption phase from blood to cerebrospinal fluid (CSF, Plasma_Tmax: 0.69 ± 0.26 h vs. CSF_Tmax: 4.0 ± 2.62 h). HSYA exhibited much higher C_max (Plasma_Cmax: 9342.76 ± 2489.23 μg/L vs. CSF_Cmax: 98.08 ± 14.51 μg/L) and AUC_0-t (Plasma_AUC0-t: 57490.5 ± 5560.3 μg h/L vs. CSF_AUC0-t: 1851.6 ± 269.1 μg h/L), yet a shorter CL (Plasma_CL: 0.02 ± 0.002 L/h/kg vs. CSF_CL: 0.55 ± 0.01 L/h/kg) in plasma than in CSF. The AUC_CSF/AUC_plasma of HSYA was almost 3.37%.

4. In summary, the results demonstrate that part of HSYA come across blood-brain barrier after XBJ administration. This study provides evidence for better understanding the pharmacokinetics and potential for clinical guidance of XBJ for TBI treatment.

Keywords:

• Hydroxysafflor yellow A
• Xuebijing injection
• pharmacokinetics
• traumatic brain injury
• biological fluids

Author contributions

Yang Wang designed the research; Chenxia Sheng, Weijun Peng, Yang Wang and Zian Xia performed the study; Yang Wang and Chenxia Sheng analysed the data; Chenxia Sheng and Yang Wang wrote and revised the paper.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported by supported by the National Natural Science Foundation of China (No. 81673719), and the Project funded by China Postdoctoral Science Foundation (Nos. 2017T100614 and 2016M600639).