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.

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.

Cerebrospinal fluid hypocretin (orexin) levels are elevated by play but are not raised by exercise and its associated heart rate, blood pressure, respiration or body temperature changes.

Hypocretin (Hcrt) has been implicated in the control of motor activity and in respiration and cardiovascular changes. Loss of Hcrt in narcolepsy is linked to sleepiness and to cataplexy, a sudden loss of muscle tone which is triggered by sudden strong emotions. In the current study we have compared the effects of treadmill running, to yard play on cerebrospinal fluid (CSF) Hcrt level in normal dogs. We find that treadmill locomotion, at a wide range of speeds, does not increase Hcrt level beyond baseline, whereas yard play produces a substantial increase in Hcrt, even though both activities produce comparable increases in heart rate, respiration and body temperature. We conclude that motor and cardiovascular changes are not sufficient to elevate CSF levels of Hcrt and we hypothesize that the emotional aspects of yard play account for the observed increase in Hcrt.