Srivastava A K, Malik J K
Department of Pharmacology & Toxicology, College of Veterinary Science, Punjab Agricultural University, Ludhiana, India.
J Vet Pharmacol Ther. 2001 Feb;24(1):15-21. doi: 10.1046/j.1365-2885.2001.00301.x.
In the present study, the pharmacokinetics of 2-pyridine aldoxime (2-PAM, 30 mg/kg, i.v.) alone and in conjunction with atropine (0.3 mg/kg; 1/4 i.v., 3/4 i.m.) was investigated in 10 Bubalus bubalis intoxicated with a single oral lethal dose of fenitrothion (435 mg/kg). Based on the kinetic parameters, an appropriate dosage regimen of 2-PAM in B. bubalis was calculated. There was no significant difference between plasma levels and pharmacokinetic parameters of 2-PAM in the two groups of animals, given 2-PAM alone and in conjunction with atropine. The peak plasma concentration of 2-PAM at 1 min was in the range of 189.5-196.6 microg/mL which declined to 9.22-9.98 microg/mL at 4 h. The values of elimination half-life, Vd(area) and total body clearance were 2.41-2.67 h, 0.77-0.95 L/kg and 227.5-245.7 mL/kg/h, respectively. The binding capacity of 2-PAM to plasma proteins of fenitrothion-intoxicated buffalo calves and dissociation rate constant of protein drug complex were 0.015 x 10(-6) mol/g and 2.367 x 10(-6) mol, respectively. Approximately 63% of 2-PAM was bound with plasma proteins. In the treatment of organophosphate insecticide (OPI) toxicity in B. bubalis, an appropriate i.v. dosage regimen of 2-PAM in conjunction with atropine would be 18 mg/kg followed by 15 mg/kg at 4 h interval.
在本研究中，对10头经口给予单剂量致死量杀螟硫磷（435mg/kg）中毒的水牛，研究了单独静脉注射2-吡啶醛肟（2-PAM，30mg/kg）以及与阿托品（0.3mg/kg；1/4静脉注射，3/4肌肉注射）联合使用时的药代动力学。根据动力学参数，计算了水牛体内2-PAM的合适给药方案。单独给予2-PAM和与阿托品联合给予的两组动物中，2-PAM的血浆水平和药代动力学参数无显著差异。2-PAM在1分钟时的血浆峰浓度为189.5 - 196.6μg/mL，4小时时降至9.22 - 9.98μg/mL。消除半衰期、表观分布容积（Vd(area)）和全身清除率的值分别为2.41 - 2.67小时、0.77 - 0.95L/kg和227.5 - 245.7mL/kg/h。2-PAM与杀螟硫磷中毒水牛犊牛血浆蛋白的结合能力和蛋白-药物复合物的解离速率常数分别为0.015×10⁻⁶mol/g和2.367×10⁻⁶mol。约63%的2-PAM与血浆蛋白结合。在治疗水牛有机磷杀虫剂（OPI）中毒时，2-PAM与阿托品联合使用的合适静脉给药方案为18mg/kg，随后每隔4小时给予15mg/kg。
