摘要
目的探索脉搏波记录在镇静催眠药临床试验药效学和安全性评价中应用的可行性。方法研究对象为首都医科大学附属北京友谊医院研究型病房于2022年4月11日至6月11日公开招募的男性健康受试者。基于药代动力学参数分析装置,计算单用药和联合用药后咪达唑仑的药代动力学参数。记录试验期间不良事件发生情况。健康受试者在未用药、单用咪达唑仑、咪达唑仑联用伊曲康唑3种状态下,分别佩戴脉搏波记录手表24 h,记录受试者心率和体动数据,对睡眠时间、睡眠深度和多梦易醒等药效学评价指标和精神状态、昼夜节律和生命活力等安全性评价指标进行比较。结果共纳入男性健康受试者12名,年龄(34±6)岁。单用咪达唑仑时受试者中位T_(max)为0.5 h,C_(max)为(19.10±5.35)μg/L,AUC_(0-t)为(45.41±13.88)min·μg/L,AUC_(0-∞)为(46.99±14.74)min·μg/L。联用伊曲康唑后,咪达唑仑的中位T_(max)仍为0.5 h;C_(max)为(61.05±19.0)μg/L,AUC_(0-t)为(394.36±60.26)min·μg/L,AUC_(0-∞)为(553.10±178.87)min·μg/L。咪达唑仑联用伊曲康唑与单用咪达唑仑AUC_(0-t)几何均值比值的90%置信区间为735.24%~1061.57%。12名受试者中有9名共发生26例次不良事件,均为轻度。脉搏波记录结果显示,未用药、单用咪达唑仑和咪达唑仑联合伊曲康唑受试者的睡眠时间[(5.40±1.35)、(6.50±1.85)和(8.05±0.8)h,P=0.001]、睡眠深度评分[(14.13±5.15)、(19.00±4.62)和(24.32±3.66)分,P=0.005]及生命活力评分[40.00(38.00,41.00)、36.50(35.25,38.75)和32.50(30.00,36.00)分,P<0.001]的差异均有统计学意义。结论脉搏波记录针对镇静催眠药临床试验的药效学和安全性可进行实时、客观、定量评估。
Objective To explore the feasibility of pulse wave recording in the pharmacodynamics and safety evaluation in clinical trials of sedative-hypnotics.Methods The subjects were male healthy subjects who were publicly recruited by the research ward of Beijing Friendship Hospital,Capital Medical University from April 11 to June 11,2022.The pharmacokinetic parameters of the single or combined use of midazolam were calculated based on the pharmacokinetic parameter analysis set.The occurrence of adverse events during the trial were recorded.Healthy subjects wore pulse wave recording watches for 24 hours in states of without medication,midazolam alone,and midazolam combined with itraconazole,and the subjects′heart rate and body movement data were recorded,and pharmacodynamic evaluation indicators such as sleep duration,sleep depth and multiple dreams were compared with safety evaluation indicators such as mental state,circadian rhythm and life vitality.Results A total of 12 healthy male subjects were included,aged(34±6)years.When using midazolam alone,the median T_(max) was 0.5 hour,C_(max) was(19.10±5.35)μg/L,AUC_(0-t) was(45.41±13.88)min·μg/L,and AUC_(0-∞)was(46.99±14.74)min·μg/L.After combination with itraconazole,the median T_(max) was still 0.5 hour,C_(max) was(61.05±19.0)μg/L,AUC_(0-t) was(394.36±60.26)min·μg/L,and AUC_(0-∞)was(553.10±178.87)min·μg/L.The 90%confidence interval for the geometric mean ratio of the AUC_(0-t) between midazolam combined with itraconazole and midazolam alone was 735.24%to 1061.57%.Among the 12 subjects,9 had a total of 26 adverse events,all of which were mild.The results of pulse wave recording showed statistically significant differences in sleep duration[(5.40±1.35),(6.50±1.85),and(8.05±0.8)hours,P=0.001],sleep depth[(14.13±5.15),(19.00±4.62),and(24.32±3.66)points,P=0.005]and life vitality[40.00(38.00,41.00),36.50(35.25,38.75),and 32.50(30.00,36.00)points,P<0.001]in subjects in states of without medication,midazolam alone,and midazolam combined with itracona
作者
张健雄
陈敬成
李江硕
李丽君
吴小芳
张启明
董瑞华
Zhang Jianxiong;Chen Jingcheng;Li Jiangshuo;Li Lijun;Wu Xiaofang;Zhang Qiming;Dong Ruihua(Research Ward,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;Medical Experimental Center,China Academy of Chinese Medical Sciences,Beijing 100700,China)
出处
《药物不良反应杂志》
CSCD
2023年第9期551-555,共5页
Adverse Drug Reactions Journal
基金
北京市中医局中医药科技发展资金项目(BJZYQN-2023-01)。
