Chinese Journal of Pharmacology and Toxicology 2017;31(6):670-674

doi:10.3867/j.issn.1000-3002.2017.06.025

Absorption, distribution and excretion of 2-fluorine-6-trifl-uoromethylpyridine in rats by radioactivity isotope tracing method

Lihong LIN ; Yang YU ; Xiaolei LI ; Na LI ; Yanan PANG

Keywords

2-fluorine-6-trifluoromethylpyridine; radioactive isotope; toxicokinetics

Country

China

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.