Li Pengfei, Hoppmann Susan, Du Ping, Li Huiling, Evans Paul M, Moestue Siver A, Yu Weiyue, Dong Fang, Liu Hongchuan, Liu Lihong
Phase I Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, China.
GE Healthcare, The Grove Centre, Amersham, Buckinghamshire, UK.
Ultrasound Med Biol. 2017 May;43(5):1031-1039. doi: 10.1016/j.ultrasmedbio.2017.01.003. Epub 2017 Mar 7.
Sonazoid is an ultrasound contrast agent based on microbubbles (MB) containing perfluorobutane (PFB) gas. Sonazoid is approved in Japan, Korea and Norway for contrast-enhanced ultrasonography of focal liver lesions and focal breast lesions (Japan only). The objective of this study was to determine the pharmacokinetics (PKs) and safety of Sonazoid in Chinese healthy volunteers (HVs) and to evaluate the potential for ethnic differences in PKs between Chinese and Caucasian HVs. Sonazoid was administered as an intra-venous bolus injection at the clinical dose of 0.12 μL or 0.60 μL MB/kg body weight to two groups of eight Chinese HVs. Expired air and blood samples were collected and analyzed using a validated gas chromatographic tandem mass spectrometry method, and the main PK parameters were calculated. The highest PFB concentrations in blood were observed shortly after intra-venous administration of Sonazoid, and elimination of PFB was rapid. In the 0.12 μL MB/kg body weight cohort, PFB concentrations above the limit of quantification were observed for only 10 to 15 min post-injection. In the 0.60 μL MB/kg body weight cohort, PFB concentrations above the limit of quantification were observed for 60 min post-injection, and the shape of the elimination curve suggested a biphasic elimination profile. The maximum observed concentration (C) values of PFB in blood were 2.3 ± 1.1 and 19.1 ± 9.2 ng/g for the 0.12 and 0.60 μL MB/kg body weight dose groups (mean ± standard deviation). Area under the curve values were 10.1 ± 2.7 and 90.1 ± 38.3 ng × min/g for the 0.12 and 0.60 μL MB/kg body weight dose groups. C values of PFB in exhaled air were 0.35 ± 0.2 and 2.4 ± 0.7 ng/mL for the 0.12 and 0.60 μL MB/kg body weight dose groups. Assessment of laboratory parameters, vital signs, oxygen saturation and electrocardiograms revealed no changes indicative of a concern. The PK profile and safety data generated in the Chinese HVs were comparable to previous data for Caucasian HVs.
舒血管素是一种基于含有全氟丁烷（PFB）气体的微泡（MB）的超声造影剂。舒血管素在日本、韩国和挪威被批准用于肝脏局灶性病变和乳腺局灶性病变（仅日本）的超声造影检查。本研究的目的是确定舒血管素在中国健康志愿者（HV）中的药代动力学（PK）和安全性，并评估中国和白种人HV在PK方面种族差异的可能性。以0.12μL或0.60μL MB/kg体重的临床剂量静脉推注舒血管素，分别给予两组各8名中国HV。收集呼出气体和血液样本，采用经过验证的气相色谱串联质谱法进行分析，并计算主要的PK参数。静脉注射舒血管素后不久，血液中观察到最高的PFB浓度，且PFB的消除迅速。在0.12μL MB/kg体重组中，注射后仅10至15分钟观察到PFB浓度高于定量限。在0.60μL MB/kg体重组中，注射后60分钟观察到PFB浓度高于定量限，消除曲线形状显示为双相消除模式。0.12和0.60μL MB/kg体重剂量组血液中PFB的最大观察浓度（C）值分别为2.3±1.1和19.1±9.2 ng/g（平均值±标准差）。0.12和0.60μL MB/kg体重剂量组的曲线下面积值分别为10.1±2.7和90.1±38.3 ng×min/g。0.12和0.60μL MB/kg体重剂量组呼出气体中PFB的C值分别为0.35±0.2和2.4±0.7 ng/mL。实验室参数、生命体征、血氧饱和度和心电图评估未发现表明存在问题的变化。中国HV中产生的PK概况和安全性数据与白种人HV先前的数据相当。
