Johno I, Ludwick B T, Levy R H
J Pharm Sci. 1982 Jun;71(6):633-6. doi: 10.1002/jps.2600710609.
The pharmacokinetic profile of progabide was investigated in five chronically catheterized male rhesus monkeys. The experimental design included single-dose intravenous bolus and oral administration at two dose levels (50 and 100 mg) and zero-order intravenous infusion for 7 days. Plasma samples were analyzed by electron-capture-GLC. Protein binding of the drug was determined by equilibrium dialysis (4 degrees). A one-compartment open model with monoexponential decay was proposed to describe the pharmacokinetics. The mean parameters (+/-SEM) of the 50- and 100-mg iv bolus were: total body clearance, 2.09 (+/-0.15) and 1.53 (+/-0.18) liter/hr/kg; half-life, 0.656 (+/-0.054) and 0.789 (+/-0.079) hr; distribution volume, 1.97 (+/-0.08) and 1.79 (+/-0.21) liter/kg. Progabide was highly bound to plasma proteins and also to erythrocytes. The drug was rapidly absorbed (Tmax less than 1 hr at both doses). The mean bioavailability was attributed principally to a first-pass effect. In the constant rate infusion study, systemic clearance was larger than that of the single dose studies.
在五只长期插管的雄性恒河猴中研究了普罗加比的药代动力学特征。实验设计包括单剂量静脉推注和两种剂量水平（50和100毫克）的口服给药，以及零级静脉输注7天。血浆样本通过电子捕获气相色谱法进行分析。药物的蛋白结合通过平衡透析（4℃）测定。提出了一个具有单指数衰减的一室开放模型来描述药代动力学。50毫克和100毫克静脉推注的平均参数（±标准误）为：全身清除率，2.09（±0.15）和1.53（±0.18）升/小时/千克；半衰期，0.656（±0.054）和0.789（±0.079）小时；分布容积，1.97（±0.08）和1.79（±0.21）升/千克。普罗加比与血浆蛋白和红细胞都有高度结合。该药物吸收迅速（两种剂量下的达峰时间均小于1小时）。平均生物利用度主要归因于首过效应。在恒速输注研究中，全身清除率高于单剂量研究。
