Biessels P T, Houwertjes M C, Scaf A H, Agoston S, Horn A S
Department of Pharmacology/Clinical Pharmacology, University of Groningen, The Netherlands.
Fundam Clin Pharmacol. 1988;2(6):455-62. doi: 10.1111/j.1472-8206.1988.tb00647.x.
The pharmacokinetics, antagonistic effects, and cardiovascular effects of 2,4-diaminopyridine (2,4-DAP) were studied in 7 anaesthetized cats. Cats received a pancuronium infusion at a constant rate to cause a 90% block of contraction of the anterior tibialis muscle, stimulated through the sciatic nerve. After steady state was reached, 2,4-DAP (750 micrograms/kg IV) was administered. Plasma, urine, and bile were collected over 8 h and analyzed by means of an HPLC assay. Plasma concentrations decreased biexponentially with half-lives of 9.0 +/- 5.7 min and 140 +/- 36 min, respectively. The volume of the central compartment was 0.85 +/- 0.27 L/kg, and the volume of distribution in the steady state was 3.1 +/- 1.1 L/kg. Total plasma clearance was 18 +/- 5 ml/kg/min. Ninety percent of the administered dose was recovered in the urine and 0.1 percent in the bile in 8 h. The antagonism of the pancuronium-induced steady-state block was 98% +/- 5%, with onset and duration of 3.5 +/- 2 min and 165 +/- 40 min, respectively.
在7只麻醉猫身上研究了2,4 - 二氨基吡啶（2,4 - DAP）的药代动力学、拮抗作用及心血管效应。猫以恒定速率输注泮库溴铵，以引起胫前肌收缩被阻滞90%，通过坐骨神经进行刺激。达到稳态后，静脉注射2,4 - DAP（750微克/千克）。在8小时内收集血浆、尿液和胆汁，并通过高效液相色谱法进行分析。血浆浓度呈双指数下降，半衰期分别为9.0±5.7分钟和140±36分钟。中央室容积为0.85±0.27升/千克，稳态分布容积为3.1±1.1升/千克。总血浆清除率为18±5毫升/千克/分钟。给药剂量的90%在8小时内从尿液中回收，0.1%从胆汁中回收。泮库溴铵诱导的稳态阻滞的拮抗率为98%±5%，起效时间和持续时间分别为3.5±2分钟和165±40分钟。
