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.
Chenxia ShengWeijun PengZian XiaYang WangPublished in: Xenobiotica; the fate of foreign compounds in biological systems (2019)
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.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.A similar half-life (Plasmat1/2: 14.55 ± 3.51 h vs. CSFt1/2: 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, PlasmaTmax: 0.69 ± 0.26 h vs. CSFTmax: 4.0 ± 2.62 h). HSYA exhibited much higher Cmax (PlasmaCmax: 9342.76 ± 2489.23 μg/L vs. CSFCmax: 98.08 ± 14.51 μg/L) and AUC0-t (PlasmaAUC0-t: 57490.5 ± 5560.3 μg h/L vs. CSFAUC0-t: 1851.6 ± 269.1 μg h/L), yet a shorter CL (PlasmaCL: 0.02 ± 0.002 L/h/kg vs. CSFCL: 0.55 ± 0.01 L/h/kg) in plasma than in CSF. The AUCCSF/AUCplasma of HSYA was almost 3.37%.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.
Keyphrases
- traumatic brain injury
- cerebrospinal fluid
- blood brain barrier
- liquid chromatography tandem mass spectrometry
- severe traumatic brain injury
- end stage renal disease
- ejection fraction
- high dose
- newly diagnosed
- combination therapy
- peritoneal dialysis
- risk assessment
- ms ms
- brain injury
- rheumatoid arthritis
- mild traumatic brain injury
- replacement therapy
- adverse drug
- smoking cessation
- liquid chromatography