比格犬体内FGFC1药物代谢动力学特征及组织分布的研究  

Pharmacokinetics and tissue distribution of FGFC1,a novel marine fibrinolytic compound in Beagle dogs

作　　者：王格[1] 吴文惠[2] 王小雨[2] 张朝燕[1] 包斌[1] 

机构地区：[1]上海海洋大学食品学院,上海201306 [2]上海海洋大学海洋药物与健康食品研究所,上海201306

出　　处：《中国药理学通报》2015年第7期1019-1023,共5页Chinese Pharmacological Bulletin

基　　金：国家高技术研究发展计划资助项目(No2011AA09070109);国家自然科学基金资助项目(No81341082);上海海洋大学科技发展专项基金资助项目(No 14200069)

摘　　要：目的用高效液相色谱法(HPLC)对海洋新型纤溶化合物FGFC1(fungi fibrinolytic compound 1)的药物代谢动力学和组织分布进行成药性的初步评价。方法分析柱HPC18柱(4.6 mm×250 mm,5μm);柱温为40℃;流动相为乙腈-水(0.1%三氟乙酸)45∶55(V/V)和85∶15(V/V),流速1 m L·min-1;检测波长265 nm。前肢静脉给予比格犬3种剂量(7.5、5.0、2.5 mg·kg-1)的FGFC1,于不同的时间点取血,用HPLC测定血浆和组织中FGFC1的浓度并计算其药物代谢动力学参数和组织分布情况。结果 FGFC1的消除半衰期(T1/2β)分别为(49.035±2.171)、(48.422±2.113)及(48.811±2.372)min;达峰浓度Cmax分别为(56.48±6.23)、(48.63±5.53)、(13.64±2.76)mg·L-1;机体总消除率(CL)分别为(0.006 2±0.000 4)、(0.007 1±0.000 8)、(0.009 2±0.000 6)L·min-1·kg-1;平均保留时间(MRT)分别为(28.17±1.16)、(26.23±0.35)、(28.66±0.84)min。组织分布研究结果表明FGFC1在静脉给药后迅速分布到全身各处,最高药物浓度水平在肝脏中检出。结论FGFC1在比格犬体内呈现良好的药代动力学特性和组织分布特点,表现出较高的成药性特征,值得进一步研究。Aim To detect the concentration of the no-vel marine fibrinolytic compound FGFC1 ( fungi fi-brinolytic compound 1 ) on Beagle dogs ’ plasma and tissue by high performance liquid chromatography ( HPLC) , and also to investigate the pharmacokinetics and tissue distribution in Beagle dogs with intravenous injection, and to evaluate the FGFC1 into medicinal. Methods Chromatographic column: HP-C18 ( 4. 6 mm × 250 mm,5 μm); the column temperature was 40℃;the mobile phase was acetonitrile -0. 1% triflu-oroacetic acid gradient elute, the flow rate of 1 mL· min-1; the ultraviolet detection wavelength was 265 nm. The dog plasma samples were collected at different intervals after intravenous injection of three different doses (7. 5, 5. 0, 2. 5 mg·kg-1 ) of FGFC1, and the concentration of FGFC1 in plasma and tissue was deter-mined by HPLC method for estimating pharmacokinetic parameters and tissue distribution. Results The pa-rameters of 7. 5, 5. 0, 2. 5 mg·kg-1 were as follows:its elimination half-life ( T1/2β) was ( 49. 035 ± 2. 171 ) , ( 48. 422 ± 2. 113 ) and ( 48. 811 ± 2. 372 ) min, respectively;the peak concentration was (56. 48 ± 6. 23 ) , ( 48. 63 ± 5. 53 ) , ( 13. 64 ± 2. 76 ) mg · L-1 , respectively;clearance rate ( CL ) was ( 0. 0062 ± 0. 0004 ) , ( 0. 0071 ± 0. 0008 ) and ( 0. 0092 ± 0. 0006) L·min-1 ·kg-1 , respectively; mean reten-tion time ( MRT ) was ( 28. 17 ± 1. 16 ) , ( 26. 23 ± 0. 35) and (28. 66 ± 0. 84) min, respectively. Tissue distribution revealed that FGFC1 could quickly distrib-uted into the heart, liver, spleen, lung, kidney, intes-tine, stomach, brain, intestine, testicle, urine and fe-ces. Interestingly, the highest drug (FGFC1) concen-tration level was detected in the liver. Conclusions The above study shows a good pharmacokinetic profile as well as a good tissue distribution, indicating a drug-gable nature of the structure. Therefore, we consider that FGFC1 is promising for further study.

关 键 词：FGFC1 药代动力学特征 组织分布 高效液相色谱 比格犬 血药浓度 

分 类 号：R-332[医药卫生] R916.4