中国临床药理学杂志2024，Vol.40Issue(19)：2885-2890,6.DOI:10.13699/j.cnki.1001-6821.2024.19.025
甲磺酸雷沙吉兰片在中国健康受试者中的生物等效性研究
Bioequivalence study of rasagiline mesylate tablets in Chinese healthy subjects
陈刚 1张丽娜 1王进 1王晓琳 1臧思琦 1王泽娟 1刘晓娜 1杜爱华 1李敏 1张娅婻 1张丹1
作者信息
- 1. 航天中心医院临床药理室,北京 100049
- 折叠
摘要
Abstract
Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90％confidence interval(CI)of the geometric mean ratio(GMR)were 94.11％-118.06％,99.22％-107.74％and 99.16％-107.44％for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00％-125.00％.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90％CI of GMR were 96.99％-101.19％and 97.17％-101.41％for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00％-125.00％.The 95％upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00％-125.00％.The incidence of adverse events in fasting and fed studies was 22.86％and 22.92％,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.关键词
甲磺酸雷沙吉兰片/高变异药物/药代动力学/生物等效性Key words
rasagiline mesylate tablet/highly variable drug/pharmacokinetics/bioequivalence分类
医药卫生引用本文复制引用
陈刚,张丽娜,王进,王晓琳,臧思琦,王泽娟,刘晓娜,杜爱华,李敏,张娅婻,张丹..甲磺酸雷沙吉兰片在中国健康受试者中的生物等效性研究[J].中国临床药理学杂志,2024,40(19):2885-2890,6.
