Bokor D, Chambers J B, Rees P J, Mant T G, Luzzani F, Spinazzi A
Bracco SpA, Medical Affairs, Milan, Italy.
Invest Radiol. 2001 Feb;36(2):104-9. doi: 10.1097/00004424-200102000-00006.
To evaluate the safety profile of SonoVue, a new echo-contrast agent based on stabilized sulfur hexafluoride (SF6) microbubbles, in healthy volunteers and in patients with chronic obstructive pulmonary disease (COPD).
Safety and tolerability of SonoVue were evaluated in 66 healthy volunteers during two placebo-controlled phase I studies (a single intravenous ascending-dose study in 36 volunteers given SonoVue doses of 0.003 to 0.12 mL/kg and a multiple-dose study in 30 subjects given cumulative doses of 0.15 to 0.6 mL/kg) and in 12 patients with COPD of various degrees of clinical severity, who were given SonoVue at a dosage of 4 mL (corresponding to 0.057 mL/kg in a 70-kg patient). Adverse events were monitored up to 48 to 72 hours after administration. All volunteers underwent extensive safety assessments (monitoring of vital signs, electrocardiogram, blood oxygen saturation, laboratory assessments, and Mini-Mental test) up to 24 to 72 hours after administration. In addition, patients with COPD underwent specific lung function tests, such as forced expiratory volume, forced vital capacity, and forced midexpiratory flow.
No serious adverse events occurred throughout the study. All nonserious adverse events were minor, mild, and rapidly self-resolving. No difference in the incidence of adverse events was observed among the various dosages of SonoVue and between SonoVue and placebo. There were no clinically significant changes in any of the safety assessments. No statistically significant differences between SonoVue and placebo were observed in mean forced expiratory volume, forced vital capacity, or forced midexpiratory flow levels. No substantial changes from baseline in blood oxygen saturation were observed for either study agent at any postinjection time point.
SonoVue showed a good safety profile both in healthy subjects and in patients with COPD.
评估新型超声造影剂声诺维（基于稳定的六氟化硫（SF6）微泡）在健康志愿者和慢性阻塞性肺疾病（COPD）患者中的安全性。
在两项安慰剂对照的I期研究中评估了声诺维的安全性和耐受性，其中一项是在36名健康志愿者中进行的单次静脉递增剂量研究（给予声诺维剂量为0.003至0.12 mL/kg），另一项是在30名受试者中进行的多次剂量研究（给予累积剂量为0.15至0.6 mL/kg）；还在12名不同临床严重程度的COPD患者中进行了研究，给予他们4 mL声诺维（相当于70 kg患者的0.057 mL/kg）。给药后长达48至72小时监测不良事件。所有志愿者在给药后长达24至72小时接受了广泛的安全性评估（监测生命体征、心电图、血氧饱和度、实验室评估和简易精神状态测试）。此外，COPD患者还进行了特定的肺功能测试，如用力呼气量、用力肺活量和用力呼气中期流速。
在整个研究过程中未发生严重不良事件。所有非严重不良事件均为轻微、轻度且迅速自行缓解。在声诺维的不同剂量之间以及声诺维和安慰剂之间，未观察到不良事件发生率的差异。任何安全性评估均未出现具有临床意义的变化。在用力呼气量、用力肺活量或用力呼气中期流速水平方面，声诺维和安慰剂之间未观察到统计学上的显著差异。在任何注射后时间点，两种研究药物的血氧饱和度均未出现与基线相比的实质性变化。
声诺维在健康受试者和COPD患者中均显示出良好的安全性。
