医学
药代动力学
药效学
药理学
Evolocumab公司
曲线下面积
胃肠病学
PCSK9
耐受性
内科学
最大值
不利影响
胆固醇
脂蛋白
低密度脂蛋白受体
载脂蛋白A1
作者
Hong Lü,Yu Zhang,Cheng‐Pang Hsu,Brian Tomlinson,Andrea Luk,Ogo Egbuna,Jianhua Wu,Bassam Abosaleem,Jitesh Rana,Maria Laura Monsalvo
出处
期刊:International Journal of Clinical Pharmacology and Therapeutics
[Dustri-Verlag Dr. Karl Feistle]
日期:2020-10-01
卷期号:58 (10): 557-564
摘要
Evolocumab, a human monoclonal antibody that binds to proprotein convertase subtilisin/kexin type 9 (PCSK9), markedly reduces low-density lipoprotein cholesterol (LDL-C). Here we characterize the pharmacokinetics, pharmacodynamics, safety, and tolerability of evolocumab manufactured at a new site administered in healthy Chinese subjects.This phase 1 study of a single subcutaneous 140-mg dose of evolocumab was conducted in healthy subjects of Chinese descent residing in Hong Kong. Subjects were followed through day 85.20 subjects (all men) were enrolled. Mean (SD) age was 26.6 (8.5) years; baseline LDL-C was 2.4 (0.7) mmol/L. Mean (SD) evolocumab maximum serum concentration (Cmax) was 14.1 (5.0) μg/mL; area under the serum drug concentration-time curve from time 0 to time of last quantifiable concentration (AUClast) was 178 (80) day×μg/mL; AUC from time 0 to infinity (AUCinf) was 187 (80) day×μg/mL; terminal half-life was 5.95 (1.76) days; median time to reach Cmax (tmax) was 4.0 days. Maximum LDL-C decrease (-57.5%) was observed on day 15 and recovered to baseline by day 57. The most common adverse events (AEs) were nasal congestion (20%), oropharyngeal pain (15%), sneezing (15%), cough (10%), upper respiratory tract infection (10%), and diarrhea (10%). Most AEs were isolated incidences of mild severity, with no serious or treatment-related events. No anti-evolocumab antibodies were detected.A single 140-mg dose of evolocumab manufactured at the new site and administered in healthy Chinese subjects was associated with typical antibody pharmacokinetics, rapid and reversible decreases in LDL-C, and no new safety events.
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