用小鼠急性死亡率法测定山莨菪碱的表观药动学参数

用小白鼠急性死亡率法测定了山莨菪碱ip时的经时过程和药动学参数。山莨菪碱在小鼠体内的经时过程为二室开放模型,1.5h之前为分布相,1.5h之后为消除相。用最小二乘法和残余量法求得α、β、A和B四项表现动力学参数分别为3.608h~(-1),0.238h~(-1),529mg/kg(200.2％)和 95mg/kg(35.9％);按药动学公式分别求得分布相表观半寿期(t_(1/2)α)和消除相表现半寿期(t_(1/2)β)为0.2h和2.9h,表观转运速率常数k_(12),k_(21)和k_(10)分别为1.952h~(-1),0.749h~(-1)和1.144h~(-1);表观曲线下面积(AUC)是546mg.h/kg;表观清除率(CI)是0.48kg/(kg.h),表观分布容积V_c,V_p,V_t,和V_b分别为0.42kg/kg,1.10kg/kg,1.53kg/kg和2.04kg/kg.

Determination of apparent pharmacokinetic parameters of anisodamine by acute mortality of mice

Apparent pharmaco-kinetic parameters of anisodamine, a postganglionic cholinergic blocking agent, were determined by acute mortality of animals. (1) The ip LD50 and 95 % confidence limit in mice were determined by Karber's method, and a log dose-death probit straight line (D-P line) was drawn, and then, an appropriate dose was selected according to the D-P line. (2) The chosen dose was given twice ip into groups of mice at an interval of 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 or 12.0 hours. (3)The mortality of each interval group given 2 dosages was recorded and its corresponding dose was found from the above-mentioned D-P line.Residual % after the first dosage=(Corresponding dose-Given dose/Given dose)×100%On the basis of "interval time-residual % relationship", a curve of dynamic change in residual % after initial dosage was drawn, to make the diagram would be a straight line in elimination phase by putting residual % in log. (4) Apparent rate con- stants were calculated by least-squares regression procedure and residual method. Pharmacokinetic parameters were calculated by phar-macokinetic formulas.By this method, distribution and elimination phase of a two compartment models can be seen before and after 1.5 hours respectively. Their pharmacokinetic parameters are: apparent rate constants of distribution phase and elimination phase, 3.608 h-1 and 0.238 h-1, respectively; the apparent residual % at zero hour of distribution phase and elimination phase, 200.2 and 35.9, respectively; their corresponding residual amounts, 529 mg/kg and 95 mg/kg, respectively; apparent half-lives of distribu-tion phase and elimination phase, 0.2 h and 2.9h, respectively; apparent AUC, 546mg·h/kg, apparent clearance, 0.48 kg/(kg·h), apparent distribution volume of center compartment Vc), 0.42 kg/kg; apparent distribution volume of peripheral compartment (vp), l.l0kg/kg; total apparent distribution volume(Vt), 1.53 kg/kg and apparent distribution volume of elimination phase (Vb), 2.04 kg/kg; apparent rate constants k12, k21 and k10, 1.952 h-1, 0.749 h-1 and 1.144h-1, respectively.