注射用石杉碱甲缓释微球单次给药在中国健康人体药代动力学研究  

Pharmacokinetics of single dose sustained release microspheres of Huperzine A for injection in Chinese healthy volunteers

作　　者：朱珍真[1] 郎丽巍[1] 王红艳[1] 王丽珍 段锋 张丽[1] 王敏[1] 宋占东 魏振满[1] ZHU Zhen-zhen;LANG Li-wei;WANG Hong-yan;WANG Li-zhen;DUAN Feng;ZHANG Li;WANG Min;SONG Zhan-dong;WEI Zhen-man(Drug Clinical Trial Center,302 Military Hospital of China,Beijing 100039,China)

机构地区：[1]中国人民解放军第三〇二医院药物试验中心,北京100039

出　　处：《中国临床药理学杂志》2018年第20期2441-2444,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价不同剂量注射用石杉碱甲缓释微球单次给药后在健康受试者体内的药代动力学变化。方法用随机、双盲、安慰剂对照、试验药物剂量递增的试验设计。共招募48例受试者,随机分为5组,分别单次臀部肌肉注射0. 75,1. 5,3. 0,4. 5,6. 0 mg注射用石杉碱甲缓释微球或安慰剂。给药前后按时间点采集生物样本以检测血药浓度,并计算主要药代动力学参数。结果中国健康受试者接受单次臀部注射石杉碱甲缓释微球(0. 75,1. 5,3. 0,4. 5和6. 0 mg),血浆浓度达峰时间(tmax)分别为(120. 00±41. 57),(150. 00±37. 95),(120. 00±12. 83),(105. 00±12. 42),(108. 00±18. 14) h;消除半衰期(t1/2)分别为(61. 66±20. 78),(44. 84±16. 05),(73. 73±30. 25),(41. 47±21. 65),(55. 89±18. 17) h; Cmax分别为(0. 21±0. 04),(0. 62±0. 41),(1. 18±0. 24),(2. 74±0. 47),(2. 86±0. 67)μg·L^(-1); AUC0-t分别为(41. 32±7. 02),(106. 68±66. 79),(227. 97±42. 09),(505. 01±79. 38),(541. 93±124. 47)ng·m L^(-1)·h。结论单次注射不同剂量的石杉碱甲缓释微球,其Cmax和AUC0-t随剂量增加而增加,呈现剂量比例关系;吸收速率和消除速率并未受给药剂量影响;其较长的半衰期支持在治疗时以较长的给药间隔给药。Objective To evaluate the sustained release microspheres of Huperzine A for injection single dose pharmacokinetic changes in healthy volunteers. Methods This study taken randomized, double - blind, placebo- controlled, dose escalation experiment design, 48 healthy vol- unteers were randomly divided into 5 groups, then they respectively taken orally single dose （0. 75,1.5,3.0,4. 5,6. 0 mg） sustained release mirospheres of Huperzine A for injection by intramuscular injection. Before and after administration, we taken biological samples for detection of blood drug concentration, furthermore, calculation of blood drug pharma- cokinetic parameters. Results After single dose injected 0. 75 mg, 1.5 mg,3.0 mg,4. 5 mg,6. 0 mg sustained release microspheres of Huperzine A, the main pharmacokinetic parameters -of plasma Huperzine A, tmax were （120.00± 41.57）, （150.00±37.95）, （120.00±12.83）, （ 105.00±12. 42）, （ 108.00±18. 14） h ; t1/2 were （61.66±20. 78 ）, （44.84±16.05 ）, （ 73.73±30.25 ）, （41.47±21.65）, （55.89 ±18. 17）h; CmaX were （0.21 ±0.04）,（0.62±0.41）, （1.18±0.24）, （2.74±0.47）, （2.86 ±0.67）μg· L^-l; AUC0-t,were （41.32±7.02）, （106.68±66.79）, （227.97±42.09） ,（505.01±79.38） ,（541.93 ±124. 47）ng ·mL^-1· h. Conclusion After single injection of different doses of Huperzine A sustained release microspheres, the Cmax and AUC0-t, were increased with the dose escalation, presented dose- proportional relationship, and the absorption rate and elimination rate were not affected by the dosage. The drug has a long half- life, that supports long intervals of administration during treatment.

关 键 词：石杉碱甲 缓释制剂 单次给药 药代动力学 血药浓度 

分 类 号：R97[医药卫生—药品]