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中国临床药理学与治疗学 ›› 2000, Vol. 5 ›› Issue (3): 213-217.

• 论著 • 上一篇    下一篇

蝙蝠葛碱犬体内药代动力学研究

陈淑娟, 张斌, 杨毅梅, 代宗顺, 曾繁典   

  1. 同济医科大学临床药理研究所,武汉430030
  • 收稿日期:2000-05-30 修回日期:2000-07-07 出版日期:2000-09-26 发布日期:2020-11-25
  • 作者简介:陈淑娟,女,27岁,医学博士,主要从事药物代谢动力学研究。曾繁典,男,教授,博士生导师,中国药理学会副理事长。

Pharmacokinetics of dauricine in dogs

CHEN Shu-Juan, ZHANG Bin, YANG Yi-Mei, DAI Zong-Shun, ZENG Fan-Dian   

  1. Institute of Clinical Pharmacology,Tongji Medical University,Wuhan 430030
  • Received:2000-05-30 Revised:2000-07-07 Online:2000-09-26 Published:2020-11-25

摘要: 目的 研究不同给药途径及剂量的蝙蝠葛碱(Dau)在犬体内药代动力学特征。方法 采用拉丁方设计对5 只犬进行静注、灌胃2 种给药途径及5 个剂量的实验,用HPLC-UV法测定血药浓度,计算药代动力学参数。结果 犬静注Dau 6 mg·kg-1后,药物符合二室开放模型线性动力学消除过程,t1/2(α)6~12min,K12>K21,t1/2(β)(2.7±0.4)h,Vd11.18L·kg-1。Dau灌胃给药后各犬C-T 曲线呈显著双峰现象,各剂量组tpeak(1)为(0.8±0.6)~(1.2±0.5)h,tpeak(2)为(5.2±3.2)~(6.5±1.9)h,Cmax(2)一般小于相应的Cmax(1)。在12.5~25 mg·kg-1范围Dau呈线性消除,两者t1/2(el)、CL、AUC/X0等重要药代动力学参数均无显著性差异(P>0.05),AUC随给药剂量成比例上升;在50mg·kg-1以上剂量时,药物消除呈非线性,t1/2(el)、CL、AUC/X0等重要参数显著改变(P<0.05),AUC超比例增加。结论 灌胃给药后,Dau在犬体内广泛分布并从血液中迅速清除。在50mg·kg-1以下剂量时,最大血药浓度、AUC剂量依赖性增加,药物消除呈线性特征,超过此剂量,药物t1/2(el)、CL明显延长,提示大剂量下药物消除存在饱和动力学特征。

关键词: 蝙蝠葛碱, 药代动力学, 反相高效液相色, 谱法

Abstract: Aim To study the pharmacokinetic characters of Dauricine in dogs.Methods Dauricine was applied in 5 dosages of two administration ways 5 dogs according to Latin Square plan. The drug plasma concentration was determined by RP-HPLC.Results Dauricine spread quickly from central compartment to spherical compartment after intravenous administration of 6 mg·kg-1.The t1/2 (α) was 6~12min, K12>K21.The mean t1/2 (β) was (2.7±0.4) h,Vd was about 11.18 L·kg-1.The C-T profile conformed to two compartment open model.The plasma Dau concentration-time curves showed a double-peak phenomenon in all dosages of all dogswhen dauricine was given by intragastric was.The tpeak(1)was (0.8±0.6)~(1.2±0.5)h, tpeak(2) was (5.2±3.2)~(6.5±1.9) h, Cmax(2)< Cmax(1). Dauricine was eliminated linearly in the do sages of 12.5 and 25 mg·kg-1,there was no obvious difference of parameters t1/2(el),CL,AUC/X0 between them (P>0.05)and the AUC was increased in pro portion.The drug is eliminated non-linearly when the dosage is above 50 mg·kg-1,the parameters t1/2(el), CL,A UC/X0 shows great difference (P<0.01)comparing with dosage 12.5 mg·kg-1,AUC was increased out of pro portion.Conclusion The plasma drug co ncentration-time curve of Dau afterig administration in dogs shows a double-peak phenomenon.A saturated character in Dauricine’s elimination is observed when the dosage is over or equal to 50mg·kg-1.

Key words: dauricine, pharmacokinetics, RP-HPLC

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