Absorption, distribution and excretion of 2-fluorine-6-trifl-uoromethylpyridine in rats by radioactivity isotope tracing method
10.3867/j.issn.1000-3002.2017.06.025
- VernacularTitle:放射性同位素示踪法研究2-氟-6-三氟甲基吡啶在大鼠体内的吸收、分布和排泄
- Author:
Lihong LIN
;
Yang YU
;
Xiaolei LI
;
Na LI
;
Yanan PANG
- Keywords:
2-fluorine-6-trifluoromethylpyridine;
radioactive isotope;
toxicokinetics
- From:
Chinese Journal of Pharmacology and Toxicology
2017;31(6):670-674
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To study the absorption,distribution and excretion of 2-fluorine-6-trifluoromethylpyridine (JJBD) in rats.METHODS [14C] Radioactivity isotope tracing method was used.Male SD rats were ig given a single dose of JJBD 10 and 100 mg·kg-1 (radioactivity:3.7 GBq·kg-1).Concentrations of rat plasma,tissue,feces,urine and bile were determined with a liquid scintillation counting (LSC) analyzer.Toxicokinetics (TK) parameters were fitted using WinNonlin.RESULTS TK parameters of JJBD 10 and 100 mg · kg-1 in male SD rats were as follows:area under the curve (AUC（0-t）) was 22 548±1579 and (203 395±27 586) h·iμg Eq.·L-1,half time (t1/2) was 15.8±1.0 and (14.1±0.9) h,peak time (Tmax) was 4.0±3.0 and (6.0±5.0) h,peak concentration (Cmax) was 1450±355 and (7776±1703) μg Eq.·L-1.JJBD was mainly distributed in fat,livers,kidneys,stomachs and intestinal walls.The concentration of JJBD in most of the tissues reached peak values after 4 h.However,JJBD couldn't be detected in the muscle,thymus gland,brain,gonad or spleen.Excretion rate of JJBD was 43.1％ in urine,29.7％ in feces and 9.97％ in cleaning solution within 0-168 h.JJBD could be excreted through bile at a rate of 28.1％ within 0-72 h.CONCLUSION JJBD can be absorbed immediately and excreted slowly in SD rat.There is no accumulation risk.The distribution of JJBD in vivo is very extensive,but cannot go through the blood-brain barrier.JJBD is mostly excreted through feces and urine.
