Abstract��OBJECTIVE To investigate the pharmacokinetics of matrine injection by different routes of administration. METHODS Twenty healthy SD rats were enrolled in this study. They were randomly divided into two groups and received intraperitoneal and intravenous administration of matrine injection at dose of 15 mg��kg-1 respectively. Blood samples (0.3-0.4 mL) were immediately collected into heparinized tubes before injection and at 0.033, 0.083, 0.167, 0.333, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 h after injection. Plasma sample concentrations were determined by a validated LC-MS/MS method. The pharmacokinetic parameters including AUC0-12, AUC0-��, MRT0-12, MRT0-��, t1/2, Vd, CL and ��max were calculated. RESULTS The main pharmacokinetic parameters for matrine after intraperitoneal and intravenous administration at dose of 15 mg��kg-1 were as follows:AUC0-12 (10 166��2 426), (12 217��2 968) ng��mL-1��h;AUC0-�� (10 230��2 432), (12 300��3 031)- ng��mL-1��h;MRT0-12 (1.91��0.41), (2.14��0.54) h;MRT0-�� (2.01��0.41), (2.26��0.64) h; t1/2(2.26��0.89), (2.60��1.25) h;Vd(4 998��2 010), (6 175��2 540) mL;CL (1 531��315.0), (1 727��475.6) mL��h-1��kg-1; ��max (5 246��1 187), (8 503��1 101) ng��mL-1, respectively. The bioavailability of intraperitoneal administration is 83.21%. CONCLUSION No significant differences were observed in AUC, MRT, t1/2 and CL values of matrine between different administrations except for ��max and Vd.
������, ����ϼ, ����Ӣ, ��ʦ, ������, ����Ӣ. LC-MS/MS�о���ͬ��ҩ;����μ�ע��Һ�ڴ������ڵ�ҩ��ѧ[J]. �й�ҩѧ��־, 2017, 52(4): 303-307.
FENG Xiao-jie, WANG Ming-xia, FENG Zhang-ying, ZHANG Shi, WANG Guan-qi, DU Li-ying. Pharmacokinetic Study of Matrine Injection in Rats with Different Administration Ration Routes by LC-MS/MS Method. Chinese Pharmaceutical Journal, 2017, 52(4): 303-307.
ZHANG L H, CHEN B N, PAN M J. Advances in pharmacological effects of matrine [J]. Chin Tradit Herb Drugs (�в�ҩ), 2009, 40(6):1000-1003.
[2]
ZHANG H F, SHI L J, SONG G Y,et al. Protective effects of matrine against progression of high-fructose diet-induced steatohepatitis by enhancing antioxidant and anti-inflammatory defences involving Nrf2 translocation[J]. Food Chem Toxicol, 2013, 55(5):70-77.
[3]
LIAO H, ZHAO X, QU J, et al. Matrine suppresses invasion and metastasis of NCI-H1299 cells by enhancing microRNA-133a expressi[J]. Int J Clin Exp Med, 2015, 8(7):10714-10722.
[4]
WAN X Y, LUO M, LI X D, et al. Hepatoprotective and anti-hepatocarcinogenic effects of glycyrrhizin and matrine[J]. Chem Biol Interact, 2009, 181(1):15-19.
[5]
DAI Z J, GAO J, JI Z Z, et al. Matrine induces apoptosis in gastric carcinoma cells via alteration of Fas/FasL and activation of caspase-3[J]. Ethnopharmacol, 2009,123 (1):91-96.
[6]
ZHANG J, LI Y, CHEN X, et al. Autophagy is involved in anticancer effects of matrine on SGC-7901 human gastric cancer cells[J]. Oncol Rep, 2011, 26(1):115-124.
[7]
YAN F, LIU Y, WANG W. Matrine inhibited the growth of rat osteosarcoma UMR-108 cells by inducing apoptosis in a mitochondrial-caspase-dependent pathway[J]. Tumour Biol, 2013, 34(4):2135-2140.
[8]
FENG X J, DU L Y, FENG Z Y, et al. Progress in matrix effect of determining blood concentration by LC-MS/MS[J]. Chin New Drug J (�й���ҩ��־), 2015, 24(13):1488-1492.
[9]
ZHANG L,TAN L, WANG S H, et al. Survey on off-lable uses of drugs in 24 hopitals[J]. Chin Pharm J (�й�ҩѧ��־), 2016,51(2):151-154.
[10]
ZHANG J W, DUAN D M, REN Z H. Combination of compound kushen injection and cisplatin intraperitoneal chemotherapy in patients with gastric cancer and malignant ascites[J]. Chin J Exp Tradit Med Form (�й�ʵ�鷽��ѧ��־), 2016, 22(11):179-183.
[11]
CHEN G R, LI J Y, GUO K, et al. Clinical observation on treatment of ascites due to hepatocellular carcinoma by compound kushen injection combined with intraperitoneal chemotherapy[J]. Chin J Inf Tradit Chin Med (�й���ҽҩ��Ϣ��־), 2013,20(11):66-67.
[12]
ZHANG T X, ZHAO J B, LIU R H, et al. Clinical observation of compound matrine combined with cisplatin and microwave hyper-thermia in the treatment of ovarian cancer ascites[J]. Mode Nonco J (�ִ�����ҽѧ), 2016,24(9):1443-1445.
[13]
XU S Y, BIAN R L, CHEN X. Pharmacological Experimrntal Methodology (ҩ��ʵ�鷽��ѧ)[M]. 3rd ed. Beijing:People's Medical Publishing House, 1982:181-182.
[14]
YUAN F, CHEN J, WU W J, et al. Effects of matrine and oxymatrine on catalytic activity of cytochrome p450s in rats[J]. Basic Clin Pharmacol Toxicol, 2010, 107(5):906-913.
[15]
ZHAO C G, LIAO D D, HE X Y, et al. Study on pharmacokinetics of matrine by intramuscular administration in rat[J]. China J Chin Mater Med (�й���ҩ��־), 2010, 35(10):1315-1318.
[16]
YANG Z, GAO S, YIN T, et al. Biopharmaceutical and pharmacokinetic characterization of matrine as determined by a sensitive and robust UPLC-MS/MS method[J]. J Pharm Biomed Anal, 2010, 51(5):1120-1127.
[17]
GAO G, LAW F C. Physiologically based pharmacokinetics of matrine in the rat after oral administration of pure chemical and ACAPHA[J]. Drug Metab Dispos, 2009, 37(4):884-891.
[18]
WU X, YAMASHITA F, HASHIDA M, et al. Determination of matrine in rat plasma by high-performance liquid chromatography and its application to pharmacokine studies[J]. Talanta, 2003, 59(5):965-971.