地昔尼尔乳剂在绵羊体内的药动学研究

Pharmacokinetics of dicyclanil emulsion in sheep

为建立高效液相色谱法（HPLC）测定绵羊血浆中地昔尼尔的质量浓度,比较健康绵羊经皮肤浇泼地昔尼尔乳剂和进口地昔尼尔乳剂（Clik）后的药动学特征及生物利用度,选用12头健康绵羊随机分为地昔尼尔乳剂组和Clik组,公母各半,并以35 mg·kg-1的剂量于背正中线浇泼给药,在不同时间点内于颈静脉处采血,分离血浆,采用HPLC测定地昔尼尔的血药浓度。结果显示：地昔尼尔在20-10 000 ng·mL^（-1）浓度范围内线性良好,r2〉0.999,定量限（LOQ）为20 ng·mL^（-1）;地昔尼尔以定量限、低、中、高（20、100、1 000、10 000 ng·mL^（-1））4个浓度添加水平的回收率均大于80%,精密度均小于15%;地昔尼尔乳剂组药动学参数：消除半衰期（T（1/2λz））=（25.35±7.50）h,达峰时间（T（max））=（46.00±4.90）h,达峰浓度（C（max））=（473.73±102.53）ng·mL^（-1）,药时曲线下面积（AUC（0→t））=（20 856.38±4 178.93）ng·mL^（-1）·h;Clik-组药动学参数：T（1/2λz）=（33.91±10.54）h,T（max）=（44.00±6.20）h,C（max）=（469.08±126.34）ng·mL^（-1）,AUC0→t=（23 475.42±6 845.78）ng·mL^（-1）·h;地昔尼尔乳剂的相对生物利用度为88.84%。结果表明：该方法专属性强、重复性好、灵敏度高,适用于地昔尼尔在绵羊体内的药动学研究。

This experiment was aimed to establish an assay method for determination of dicyclanil by HPLC in sheep plasma,and to compare dicyclanil emulsion with imported dicyclanil emulsion（ Clik-） about the pharmacokinetic characteristics and bioavailability in healthy sheep. Twelve healthy sheep,were chosen and randomly divided into the dicyclanil emulsion group and the Clik group,both having half males and half females. Both groups were treated with a dose of 35 mg·kg^（-1） at the midline of the back of the body,and blood samples were collected from the jugular vein at different time points,and plasma samples were separated. Then,HPLC was used to detect the concentration of dicyclanil. The results showed that dicyclanil had a good liner relationship when the concentration was at 20 to 10 000 ng·mL^（-1）（ r-20. 999）,and the limits of quantification（ LOQs） was 20 ng·mL^（-1）. Dicyclanil were added to blank plasma at four levels： quantitative limit,bottom,medium and high,of 20,100,1 000,10 000 ng·mL^（-1）,respectively,which achieved a mean recovery higher than 80% with RSD being lower than 15%. The pharmacokinetic parameters of the dicyclanil emulsion group were T（1/2λz）=（ 25. 35± 7. 50） h,T（max）=（ 46. 00±4. 90） h,C（max）=（ 473. 73±102. 53） ng·mL^（-1）,and AUC（0→t）=（ 20 856. 38 ± 4 178. 93） ng·mL^（-1）·h. Those of the Clik- group were T（1/2λz）=（ 33. 91±10. 54） h,T（max）=（ 44. 00 ± 6. 20） h,C（max）=（ 469. 08 ± 126. 34） ng · mL^（-1）,and AUC（0→t）=（ 23 475. 42 ± 6 845. 78）ng·mL^（-1）·h. The relative bioavailability was 88. 84%. To conclude,the present method was of high sensitivity,good reproducibility and specificity,and applicable to research on pharmacokinetics of dicyclanil in sheep.