Kamath B L, Stampfli H F, Lai C M, Yacobi A
J Pharm Sci. 1981 Jun;70(6):667-9. doi: 10.1002/jps.2600700623.
The pharmacokinetics of bretylium tosylate were investigated in eight male Charles River rats. Each animal received an intravenous dose (10 mg/kg) of [14C)bretylium tosylate. Serial blood samples, urine, and feces were collected for up to 72 hr. Bretylium concentrations in plasma and amounts excreted in urine and feces were determined by scintillation counting. On the average, 88 and 95% of the dose were recovered in urine and feces in 24 and 72 hr, respectively. Urinary recovery accounted for 65.6 of the dose while 29.7% was excreted in the feces. Bretylium concentrations in plasma declined triexponentially and were fitted to a three-compartment open model. Bretylium has a very high apparent volume of distribution (15 liters/kg), and its beta half-life averaged 5.5 hr. Mean values of the apparent volume of the central compartment, plasma clearance, renal clearance, and excretion rate constants of bretylium in rats were 1 liter/kg, 1.93 liters/hr/kg, 1.27 liters/hr/kg, and 1.24 hr-1, respectively. The results indicate that: (a) bretylium is strongly bound to the tissues and is eliminated by active urinary secretion and by biliary excretion in rats, and (b) there are strong similarities between the pharmacokinetics of bretylium in humans and rats and that this animal model might be suitable for interaction studies with other drugs.
在八只雄性查尔斯河大鼠中研究了甲苯磺酸溴苄铵的药代动力学。每只动物静脉注射一剂（10毫克/千克）[14C]甲苯磺酸溴苄铵。连续采集血样、尿液和粪便，长达72小时。通过闪烁计数法测定血浆中溴苄铵浓度以及尿液和粪便中的排泄量。平均而言，在24小时和72小时时，分别有88%和95%的剂量在尿液和粪便中回收。尿液回收占剂量的65.6%，而29.7%经粪便排泄。血浆中溴苄铵浓度呈三相指数下降，并拟合为三室开放模型。溴苄铵具有非常高的表观分布容积（15升/千克），其β半衰期平均为5.5小时。大鼠中溴苄铵中央室表观容积、血浆清除率、肾清除率和排泄速率常数的平均值分别为1升/千克、1.93升/小时/千克、1.27升/小时/千克和1.24小时-1。结果表明：（a）溴苄铵与组织紧密结合，在大鼠中通过主动尿分泌和胆汁排泄消除；（b）溴苄铵在人和大鼠中的药代动力学有很强的相似性，并且这种动物模型可能适用于与其他药物的相互作用研究。
