title: Pharmacokinetics of Perfluorobutane after Intra-Venous Bolus Injection of Sonazoid in Healthy Chinese Volunteers.
abstract: 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 (Cmax) 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. Cmaxvalues 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.
authors.affiliation: Phase I Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Li
authors.affiliation: GE Healthcare, The Grove Centre, Amersham, Buckinghamshire, UK. Electronic address: Susan.Hoppmann@ge.com.
authors.forename: Susan
authors.initials: S
authors.lastname: Hoppmann
authors.affiliation: Phase I Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Du
authors.affiliation: Phase I Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Li
authors.affiliation: GE Healthcare, The Grove Centre, Amersham, Buckinghamshire, UK.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Evans
authors.affiliation: Department of Laboratory Medicine, Women's and Children's Health, Faculty of Medicine, NTNU (Norwegian University of Science and Technology), Trondheim, Norway.
authors.forename: Siver A
authors.initials: SA
authors.lastname: Moestue
authors.affiliation: Phase I Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, China.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Yu
authors.affiliation: Phase I Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Dong
authors.affiliation: Phase I Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, China.
authors.forename: Hongchuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Phase I Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Liu
mesh_terms: D000328:Adult; D044466:Asian People / Q000706:statistics & numerical data; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005466:Fluorocarbons / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007564:Japan; D008297:Male; D045423:Microbubbles; D010087:Oxides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012016:Reference Values; D044465:White People / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D005466:Fluorocarbons; D010087:Oxides; C069727:Sonazoid; D007501:Iron; C108042:perfluorobutane
keywords: Microbubbles; Microspheres; Perfluorobutane; Pharmacokinetics; Sonazoid; Ultrasound