Pharmacokinetics and tissue distribution of a novel marine fibrinolytic compound in Wistar rat following intravenous administrations
Pharmacokinetics and tissue distribution of a novel marine fibrinolytic compound in Wistar rat following intravenous administrations
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DOI：
10.1016/j.jchromb.2013.10.031
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发表时间：
2013-12-30
影响因子：
3
通讯作者：
Bao, Bin
中科院分区：
文献类型：
--
作者：
Su, Tongwei;Wu, Wenhui;Bao, Bin
我们研究了一种新的海洋纤维蛋白溶解化合物用于溶栓治疗。在Wistar大鼠中静脉（IV）推注两种浓度（10和20 mg/kg）后，研究了这种新型海洋纤维蛋白溶解化合物FGFC 1（2）（真菌纤维蛋白溶解化合物1）的药代动力学和组织分布。使用具有UV检测的HPLC测量血浆FGFC 1和组织提取物。使用C-18柱检测FGFC 1，乙腈-水（0.1%三氟乙酸）梯度洗脱移动的相，1.0 mL/min。在265 nm处监测色谱图（柱温：40 ℃）。药代动力学数据表明，FGFC 1很好地符合二室模型。对于10和20 mg/kg，FGFC 1的消除半衰期（t（1/2））分别为21.51 +/- 2.17和23.22 +/- 2.11 min。AUC（0-t）为412.19 +/- 19.09，899.09 +/- 35.86 μ g/mL min，全身清除率（CL）为0.023 +/- 0.002，0.022 +/- 0.002（（mg/kg）/（μ g/mL）/min），平均滞留时间（MRT）为10.15 +/- 10.97，10和20 mg/kg剂量组分别为9.65 +/- 1.40 min。在试验剂量下未观察到全身清除率和平均滞留时间的显著差异，表明大鼠中的线性药代动力学。组织分布数据显示，FGFC 1在除脑外的大多数组织中快速分布，并且药物的最高浓度在肝脏中。在小肠中，FGFC 1最初增加，然后下降，但在给药后60分钟仍相对较高，表明可能存在肝肠循环（C）2013作者。Elsevier B. V.出版，保留所有权利。
We investigated a novel marine fibrinolytic compound for use in thrombolytic therapy. Pharmacokinetics and the tissue distribution of this novel marine fibrinolytic compound, FGFC1(2) (fungi fibrinolytic compound 1), were investigated in Wistar rats after intravenous (IV) bolus administration of two concentrations (10 and 20 mg/kg). Plasma FGFC1 and tissue extracts were measured using HPLC with UV detection. FGFC1 was detected using a C-18 column with a gradient eluted mobile phase of acetonitrile-water (0.1% trifluoroacetic acid), 1.0 mL/min. Chromatograms were monitored at 265 nm (column temperature: 40 degrees C). Pharmacokinetic data indicate that FGFC1 fitted well to a two-compartment model. Elimination half-lives (t(1/2)) of FGFC1 were 21.51 +/- 2.17 and 23.22 +/- 2.11 min for 10 and 20 mg/kg, respectively. AUC(0-t) were 412.19 +/- 19.09, 899.09 +/- 35.86 mu g/mLmin, systemic clearance (CL) was 0.023 +/- 0.002, 0.022 +/- 0.002 ((mg/kg)/(mu g/mL)/min) and the mean residence time (MRT) was 10.15 +/- 10.97, 9.65 +/- 1.40 min at 10 and 20 mg/kg, respectively. No significant differences were observed in the systemic clearance and mean residence time at the tested doses, suggesting linear pharmacokinetics in rats. Tissue distribution data reveal that FGFC1 distributed rapidly in most tissues except the brain and that the highest concentration of the drug was in the liver. In the small intestine, FGFC1 initially increased and then declined, but remained comparatively high 60 min after administration, suggesting that enterohepatic circulation may exist (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved.