PHARMACOKINETICS OF PRALIDOXIME CHLORIDE IN THE RAT
PHARMACOKINETICS OF PRALIDOXIME CHLORIDE IN THE RAT
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DOI：
10.1016/0024-3205(86)90405-4
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发表时间：
1986-12-08
期刊：
影响因子：
6.1
通讯作者：
CLARK, CR
中科院分区：
文献类型：
--
作者：
GREEN, MD;TALBOT, BG;CLARK, CR
本文研究了氯解磷定（2-PAM）在大鼠体内的药代动力学。以三种剂量（20、40或80 mg/kg）中的一种对不同组大鼠肌肉注射2-PAM。该剂量范围通常用于研究2-PAM对抗胆碱酯酶强效有机磷抑制剂中毒的疗效。在实验过程中收集个体的连续血液样品。从这些血样中，测定每只动物随时间推移的2-PAM血浆浓度。接下来，以标准药代动力学模型表示血浆浓度与时间的关系。使用开放一室模型计算各种药代动力学参数的估计值：分布容积（Vd）、最大血浆浓度（Cmax）、消除速率常数（k10）、吸收速率常数（k 01）、曲线下面积（AUC）和清除率（CL）。在药理学估计值中，当在所有剂量之间进行比较时，仅发现Cmax和AUC具有统计学显著性（p < 0.0001）;这些药代动力学估计值与剂量高度相关，分别为r = 0.998和r = 0.997。然而，当AUC和Cmax通过除以剂量进行标准化时，在转换数据中未发现显著差异。本研究的结果表明，在2-PAM治疗研究中使用的范围内，2-PAM的药代动力学与剂量呈线性相关。
The pharmacokinetics of pralidoxime chloride (2-PAM) was studied in rats. Different groups of rats were given an intramuscular injection of 2-PAM at one of three doses (20, 40, or 80 mg/kg). This range of doses is used commonly in studies concerned with the efficacy of 2-PAM against poisoning by potent organophosphorus inhibitors of cholinesterase enzyme. Individual, sequential blood samples were collected during the course of the experiment. From these blood samples the plasma concentrations of 2-PAM were determined over time for each animal. Next the relationship of plasma concentration to time was expressed in terms of a standard pharmacokinetic model. Estimates of various pharmacokinetic parameters were calculated using an open, one-compartment model: volume of distribution (Vd), maximal plasma concentration (Cmax), elimination rate constant (k10), absorption rate constant (k01), area under the curve (AUC) and clearance (CL). Of the pharmacological estimates, only Cmax and AUC were found to be statistically significant (p < 0.0001) when compared across all the doses; these pharmacokinetic estimates were highly correlated with doses with r = 0.998 and r = 0.997, respectively. However, when AUC and Cmax were normalized by dividing through by dose, no significant differences were found in the transformed data. The results of this study in rat indicate that the pharmacokinetics of 2-PAM is linearly related to dose in a range employed in therapeutic studies of 2-PAM.