Pharmacokinetics and tissue distribution of FGFC1,a novel marine fibrinolytic compound in Beagle dogs
10.3969/j.issn.1001-1978.2015.07.026
- VernacularTitle:比格犬体内FGFC1药物代谢动力学特征及组织分布的研究
- Author:
Ge WANG
;
Wenhui WU
;
Xiaoyu WANG
;
Chaoyan ZHANG
;
Bin BAO
- Publication Type:Journal Article
- Keywords:
FGFC1;
pharmacokinetics;
tissue distri-bution;
HPLC;
Beagle dogs;
plasma concentration
- From:
Chinese Pharmacological Bulletin
2015;(7):1019-1022,1023
- CountryChina
- Language:Chinese
-
Abstract:
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.
