Parmelee D J, Walovitch R C, Ouellet H S, Lauffer R B
EPIX Medical, Inc., Cambridge, Massachussetts 02142-1118, USA.
Invest Radiol. 1997 Dec;32(12):741-7. doi: 10.1097/00004424-199712000-00004.
The authors evaluate MS-325, a new albumin-targeted magnetic resonance imaging (MRI) contrast agent, for its pharmacokinetics, biodistribution, and elimination characteristics in multiple animal species.
Studies were performed in rats, rabbits, and nonhuman primates at intravenous doses ranging from 0.025 to 0.20 mmol/kg. Concentrations of MS-325 in blood, urine, feces, and organs were determined using gadolinium-153-labeled MS-325 and gamma counting or by using non-labeled MS-325 and inductively coupled plasma atomic emission spectrometry.
In rabbits and nonhuman primates, MS-325 is approximately 85% to 95% bound to serum proteins and, as a result, exhibits low volume of distribution (Vd) values, 0.11 to 0.14 L/kg, and a long elimination half-life (Te1/2), 2 to 3 hours. Some dose-dependence in the parameters is apparent in rabbits. MS-325 is eliminated primarily through the renal system in non-human primates. In contrast, the behavior of MS-325 in rats is different, exhibiting increased biliary excretion, a larger Vd value, and a shorter Te1/2.
The pharmacokinetics and elimination profile of MS-325, including vascular retention and renal excretion, are favorable for use in humans as an intravascular contrast agent for MRI.
作者评估了新型白蛋白靶向磁共振成像（MRI）造影剂MS - 325在多种动物物种中的药代动力学、生物分布及消除特性。
以0.025至0.20 mmol/kg的静脉给药剂量在大鼠、兔子和非人灵长类动物中开展研究。使用钆 - 153标记的MS - 325和γ计数法，或使用未标记的MS - 325和电感耦合等离子体原子发射光谱法测定血液、尿液、粪便及器官中MS - 325的浓度。
在兔子和非人灵长类动物中，MS - 325与血清蛋白的结合率约为85%至95%，因此分布容积（Vd）值较低，为0.11至0.14 L/kg，消除半衰期（Te1/2）较长，为2至3小时。在兔子中，这些参数存在一定剂量依赖性。在非人灵长类动物中，MS - 325主要通过肾脏系统消除。相比之下，MS - 325在大鼠中的行为有所不同，表现为胆汁排泄增加、Vd值较大且Te1/2较短。
MS - 325的药代动力学和消除特征，包括血管滞留和肾脏排泄，使其有利于作为MRI的血管内造影剂用于人体。
