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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Dau6mg·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12.5～25mg·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。
Objective To study the pharmacokinetics of Dau in different doses and routes of administration in dogs. Methods Latin square design was used to study the intravenous injection, intragastric administration and 5 doses of 5 dogs. HPLC-UV method was used to determine the plasma concentration and the pharmacokinetic parameters were calculated. Results After intravenous injection of Dau 6 mg · kg-1, the drug met the linear kinetic elimination process of two-compartment open model, with t1 / 2 (α) 6-12 min, K12> K21 and t1 / 2 (2.7 ± 0.4) h, Vd11.18 L · kg-1. The peak of C_T in dogs after dosing with Dau was significantly (P <0.05) ± 1.9) h, Cmax (2) is generally less than the corresponding Cmax (1). There was no significant difference (P> 0.05) in significant pharmacokinetic parameters such as t1 / 2 (el), CL, AUC / X0 between the two groups in the range of 12.5-25 mg · kg- The dose was increased proportionally. When the dose was above 50 mg · kg-1, the drug elimination was nonlinear. The important parameters such as t1 / 2 (el), CL and AUC / X0 were significantly changed (P <0.05). Conclusions After intragastric administration, Dau is widely distributed in dogs and rapidly cleared from the blood. At the dose of 50 mg · kg-1, the maximum plasma concentration and AUC increased in a dose-dependent manner, and the drug elimination showed a linear characteristic. Exceeding this dose, the drug t1 / 2 (el) and CL prolonged significantly, Saturated kinetic characteristics.