Liao Weiguo, Huang Xiaojie, Yin Yongxin, Liu Bin, Zhu Runzhi
Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, People's Republic of China.
Department for Cell Therapy center, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
Biomed Chromatogr. 2018 Jun;32(6):e4210. doi: 10.1002/bmc.4210. Epub 2018 Mar 2.
Tetramethylpyrazine (TMP) has been widely used in the treatment of ischemic cerebrovascular disease. However, the mechanism of TMP and how to increase its bioavailability need to be further explored. In our study, an in vivo microdialysis sampling technique coupled with ultra-performance liquid chromatography-mass spectrometry method was developed to investigate the pharmacokinetic properties of TMP and its interaction with different doses of borneol (BO) in rats. Linearity of TMP in brain and blood dialysates exhibited good linear relationships over the concentration range of 0.991-555.14 ng/mL. The specificity, linearity, accuracy, precision, matrix effect and stability were within acceptable ranges. The results demonstrated that BO had a marked impact on the pharmacokinetic properties of TMP. After co-administration, the areas under the concentration-time curve (AUC) of TMP in brain and blood were significantly increased. Meanwhile, the peak concentration of TMP in brain was also enhanced. The AUC /AUC of TMP, increased from 44% to 56 and 60.8% after co-administration with BO (15 and 30 mg/kg). The pharmacodynamic results showed that TMP co-administration with BO enhanced the cerebral blood flow during the period of ischemia and reduced the infarct volume. Overall, it might be an effective way to treat stroke to use TMP co-administered with BO.
川芎嗪（TMP）已广泛应用于缺血性脑血管疾病的治疗。然而，川芎嗪的作用机制以及如何提高其生物利用度仍有待进一步探索。在我们的研究中，开发了一种体内微透析采样技术结合超高效液相色谱-质谱法，以研究川芎嗪在大鼠体内的药代动力学特性及其与不同剂量冰片（BO）的相互作用。川芎嗪在脑和血液透析液中的线性在0.991 - 555.14 ng/mL浓度范围内呈现良好的线性关系。特异性、线性、准确性、精密度、基质效应和稳定性均在可接受范围内。结果表明，冰片对川芎嗪的药代动力学特性有显著影响。联合给药后，川芎嗪在脑和血液中的浓度-时间曲线下面积（AUC）显著增加。同时，川芎嗪在脑中的峰浓度也有所提高。与冰片（15和30 mg/kg）联合给药后，川芎嗪的AUC/AUC从44%分别增加到56%和60.8%。药效学结果表明，川芎嗪与冰片联合给药可在缺血期间增加脑血流量并减少梗死体积。总体而言，川芎嗪与冰片联合使用可能是治疗中风的一种有效方法。
