阿兹夫定片在健康成年及老年受试者中单次和多次给药的药代动力学研究
Pharmacokinetics study of single and multiple doses of azvudine in healthy young and elderly subjects
张宇 1刘小健 1鞠浩爽 1何斌源 2万元浩 2柴立维 3任乐阳 3吕敏 3贾亚强 4张微 4徐萍1
作者信息
- 1. 天津市第五中心医院Ⅰ期临床试验研究室,天津 300450
- 2. 河南真实生物科技有限公司,河南平顶山 467000
- 3. 有济(天津)医药科技有限公司,天津 300000
- 4. 天津洛必塔医学研究有限公司,天津 300000
- 折叠
摘要
目的 评价单次口服和多次口服阿兹夫定片在中国健康成年及老年受试者中的药代动力学特征及安全性.方法 本研究采取开放、平行方案设计.试验分为2个试验组:健康成年受试者组和健康老年受试者组,分别入组12例受试者.入组的受试者首先进行单次给药,空腹口服阿兹夫定片5 mg,经3 d清洗期后进入多次给药阶段,空腹口服阿兹夫定片5 mg·d-1,连续给药7 d.结果 单次给予阿兹夫定片5 mg后,健康成年受试者Cmax,AUC0-∞分别为(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,Tmax,t1/2 的中位数分别为0.75,1.87 h;健康老年受试者平均Cmax,AUC0-∞分别为(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,Tmax,t1/2的中位数分别为0.63,2.66 h.连续7d 给予阿兹夫定片5 mg后,健康成年受试者Cmax,ss,AUC0-∞ss分别为(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,Tmax,ss,J1/2,ss的中位数分别为0.88,2.13 h;健康老年受试者平均Cmax,ss,AUC0-∞,ss分别为(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,Tmax,ss,t1/2,ss 的中位数分别为0.75,2.56 h.单次给药后,健康老年人和健康成年人Cmax、AUC0-t和AUC0-∞的几何均数比值及其90％置信区间分别为128.37％(88.23％～186.76％)、139.93％(105.42％～185.72％)、140.03％(106.33％～184.41％).连续 7 d给予阿兹夫定片5 mg,健康老年人和健康成年人Cmax,ss、AUC0-t,ss和AUC0-∞,ss的几何均数比值及其90％置信区间分别为118.66％(80.83％～174.20％)、118.41％(83.60％～167.69％),118.95％(84.78％～166.89％).结论 单次及多次口服阿兹夫定片后,健康老年人与健康成年人相比,系统暴露均有所提高.健康老年人服用阿兹夫定片后,其不良事件和药物不良反应发生的种类、严重程度和发生率与健康成年人相比无明显差异,安全性耐受性良好.
Abstract
Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.
关键词
阿兹夫定片/老年受试者/健康成年受试者/药代动力学Key words
azvudine/elderly subjects/healthy young subjects/pharmacokinetics引用本文复制引用
出版年
2024
国家科技期刊平台
NSTL
万方数据