Feasibility study on the application of pulse wave recording in clinical trials of sedative-hypnotics
10.3760/cma.j.cn114015-20230612-00422
- VernacularTitle:脉搏波记录在镇静催眠药临床试验中应用的可行性研究
- Author:
Jianxiong ZHANG
1
;
Jingcheng CHEN
;
Jiangshuo LI
;
Lijun LI
;
Xiaofang WU
;
Qiming ZHANG
;
Ruihua DONG
Author Information
1. 首都医科大学附属北京友谊医院研究型病房，北京 100050
- Publication Type:Journal Article
- Keywords:
Hypnotics and sedatives;
Midazolam;
Clinical trials;
Safety;
Pulse wave recording;
Pharmacodynamics
- From:
Adverse Drug Reactions Journal
2023;25(9):551-555
- CountryChina
- Language:Chinese
-
Abstract:
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 Tmax was 0.5 hour, Cmax 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 Tmax was still 0.5 hour, Cmax 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 1 061.57%. 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 itraconazole. Conclusion:Pulse wave recording can be used for a real-time, objective, quantitative assessment of the pharmacodynamics and safety of sedative-hypnotics.
