Pharmacokinetics of perfluorobutane following intravenous bolus injection and continuous infusion of sonazoid™ in healthy volunteers and in patients with reduced pulmonary diffusing capacity
Pharmacokinetics of perfluorobutane following intravenous bolus injection and continuous infusion of sonazoid™ in healthy volunteers and in patients with reduced pulmonary diffusing capacity
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DOI：
10.1016/j.ultrasmedbio.2007.09.019
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发表时间：
2008-03-01
影响因子：
2.9
通讯作者：
Skotland, Tore
中科院分区：
文献类型：
--
作者：
Landmark, Kristin Eitrem;Johansen, Per Wiik;Skotland, Tore
静脉注射超声造影剂Sonazid(TM)。健康志愿者及肺弥散功能减退患者按1.2MU L微泡/Kg体重推注或连续滴注30min以上。采集了32名受试者的呼出空气和血液样本，并用有效的气相色谱-质谱法分析了全氟丁烷(PFB)气体。PFB血药浓度呈双相下降，分布半衰期(t(05)~15)为2~3min，消除半衰期(t(15~120))为30~45min。气体弥散受损患者的曲线下面积(AUC)值明显大于健康志愿者。呼气动力学变化较大，全氟苯消除半衰期(t(05)~120)为28~111min。PFB的清除与研究人群和给药方式无关。没有死亡，也没有严重的不良事件导致受试者退出研究。除了关节痛在健康志愿者中占主导地位外，无论Sonazid(TM)是作为团注还是作为输液使用，健康志愿者和患病受试者都没有表现出不同的不良事件情况。对实验室参数(血清生化、血液学和尿液分析)、生命体征、血氧饱和度和心电图(ECGs)的评估显示，没有引起安全担忧的变化。
The ultrasound contrast agent Sonazoid (TM) was administered as an i.v. bolus injection of 0.6 mu L microbubbles/kg body weight or as a continuous infusion over 30 min at a rate of 1.2 mu L microbubbles/kg body weight to healthy volunteers and patients with reduced pulmonary diffusing capacity. Expired air and blood samples were collected from 32 subjects and perfluorobutane (PFB) gas was analyzed using validated gas chromatography mass spectrometry methods. Blood concentrations of PFB declined biphasicly with a distribution half-life (t(05) (to 15)) of 2 to 3 min and an elimination half-life (t(15 to 120)) of 30 to 45 min. Area under the curve (AUC) values in patients with impaired gas diffusion were significantly larger than those in healthy volunteers. The exhalation kinetics were somewhat variable with a PFB elimination half-life (t(05) (to 120)) of 28 to 111 min. Clearance of PFB was independent of study population and mode of administration. There were no deaths and no serious adverse events that resulted in the withdrawal of a subject from the study. With the exception that arthralgia predominated in healthy volunteers, healthy volunteers and diseased subjects did not show a different adverse event profile whether Sonazoid (TM) was administered as a bolus injection or as an infusion. Assessment of laboratory parameters (serum biochemistry, haematology and urinalysis), vital signs, oxygen saturation and electrocardiograms (ECGs) showed no changes which caused safety concern.