Ingwersen S H, Petri K C, Tandon N, Yoon K-H, Chen L, Vora J, Yang W
Novo Nordisk A/S, Søborg, Denmark.
Novo Nordisk A/S, Søborg, Denmark.
Diabetes Res Clin Pract. 2015 Apr;108(1):113-9. doi: 10.1016/j.diabres.2015.01.001. Epub 2015 Jan 19.
To investigate the population pharmacokinetics and exposure-response relationship of liraglutide, a human glucagon-like peptide-1 (GLP-1) analogue, in Asian subjects with Type 2 diabetes mellitus.
Data were derived from a published 16-week, randomized, double-blind, double-dummy, active-controlled, parallel-group trial of liraglutide in China, India and South Korea. The analysis utilized 2061 pharmacokinetic (PK) samples from 605 subjects exposed to liraglutide 0.6, 1.2 or 1.8 mg once daily. Demographic factors (body weight, age, gender, country) of importance for liraglutide clearance were evaluated. An exploratory exposure-response analysis was conducted to investigate effects on glycated haemoglobin (HbA1c) and body weight.
Estimated liraglutide exposure (area under the curve; AUC) appeared to increase proportionally with increasing liraglutide dose (0.6-1.8 mg). The covariate analysis confirmed previous findings in a global clinical trial. Body weight was a predictor of liraglutide exposure; compared to a reference subject of 67 kg, exposure was 32% lower for maximum (115 kg) and 54% higher for minimum (37 kg) observed body weights. Gender, age and country had no relevant effect on exposure. Exposure-response analysis supported the use of 1.2mg as maintenance dose with the option of individual dose escalation to 1.8 mg to optimize treatment outcomes.
Exposure appeared to increase proportionally with increasing liraglutide dose in Asian subjects with Type 2 diabetes mellitus. The only PK relevant predictor of exposure was body weight. The exposure-response relationships for HbA1c and body weight in Asian subjects were similar to observations in global populations.
研究人胰高血糖素样肽-1（GLP-1）类似物利拉鲁肽在亚洲2型糖尿病患者中的群体药代动力学及暴露-反应关系。
数据来源于一项已发表的利拉鲁肽在中国、印度和韩国进行的为期16周的随机、双盲、双模拟、活性对照、平行组试验。分析使用了来自605名接受每日一次0.6、1.2或1.8mg利拉鲁肽治疗的受试者的2061份药代动力学（PK）样本。评估了对利拉鲁肽清除率重要的人口统计学因素（体重、年龄、性别、国家）。进行了探索性暴露-反应分析以研究对糖化血红蛋白（HbA1c）和体重的影响。
利拉鲁肽暴露量估计值（曲线下面积；AUC）似乎随利拉鲁肽剂量增加（0.6 - 1.8mg）而成比例增加。协变量分析证实了全球临床试验中的先前发现。体重是利拉鲁肽暴露的预测因素；与67kg的参考受试者相比，观察到的最大体重（115kg）时暴露量低32%，最小体重（37kg）时暴露量高54%。性别、年龄和国家对暴露无相关影响。暴露-反应分析支持使用1.2mg作为维持剂量，并可选择将个体剂量增至1.8mg以优化治疗效果。
在亚洲2型糖尿病患者中，暴露量似乎随利拉鲁肽剂量增加而成比例增加。暴露唯一相关的PK预测因素是体重。亚洲受试者中HbA1c和体重的暴露-反应关系与全球人群的观察结果相似。
