Wagner J G, Weidler D J, Hallmark M R, Black K L, Domino E F
Res Commun Chem Pathol Pharmacol. 1977 Feb;16(2):375-84.
In eight experiments involving four cats, doses of 12.5 to 50 mg of sodium pentobarbital per kg of body weight were administered intravenously and pentobarbital plasma concentrations (from arterial blood) were measured as a function of time. Pharmacokinetic linearity was evidenced by a mean plasma clearance (C1p) of 1.81 ml/(kg x min), with a coefficient of variation of 16.6%, and a range of 1.51 to 2.36 for all experiments, and, a linear relationship between total area under the curve (AUC) and mg/kg dose in cat "4 given doses of 12.5, 25 and 50 mg/kg. However, the apparent elimination half-life, (t1/2)beta' averaged 4.87 hr, with a coefficient of variation of 40.7%, and range of 1.80 to 7.52 in all experiments, and, in cat "4 the half-life was the same, namely 7.5 hr following the two higher doses, but lower, namely 4.7 hr, after the lowest dose. There was also evidence of kinetic nonlinearity in the intial fall-off portions of some of the curves. Results are compared with literature data for both rabbits anamen. The order of plasma clearances in units of ml/(kg x min) were: rabbit greater than cat greater than man. For neither the rabbit nor the cat were there any significant correlations between calculated pharmacokinetic parameters and mg/kg doses using data from all animals studied; this also suggests kinetic linearity.
在涉及四只猫的八项实验中,按每千克体重12.5至50毫克的剂量静脉注射戊巴比妥钠,并测量戊巴比妥血浆浓度(来自动脉血)随时间的变化。药代动力学线性表现为平均血浆清除率(C1p)为1.81毫升/(千克×分钟),变异系数为16.6%,所有实验的范围为1.51至2.36,并且在给予12.5、25和50毫克/千克剂量的猫“4”中,曲线下总面积(AUC)与毫克/千克剂量之间呈线性关系。然而,表观消除半衰期(t1/2)β平均为4.87小时,变异系数为40.7%,所有实验的范围为1.80至7.52,并且在猫“4”中,半衰期相同,即两次较高剂量后为7.5小时,但最低剂量后较低,即4.7小时。在一些曲线的初始下降部分也有动力学非线性的证据。将结果与兔和人的文献数据进行了比较。以毫升/(千克×分钟)为单位的血浆清除率顺序为:兔>猫>人。使用所有研究动物的数据,无论是兔还是猫,计算出的药代动力学参数与毫克/千克剂量之间均无显著相关性;这也表明存在动力学线性。