Chronopharmacokinetic Study with Prolonged Infusion of Midazolam
作者:
Ulrich Klotz,
Ingrid W. Reimann,
期刊:
Clinical Pharmacokinetics
(ADIS Available online 1984)
卷期:
Volume 9,
issue 5
页码: 469-474
ISSN:0312-5963
年代: 1984
出版商: ADIS
数据来源: ADIS
摘要:
Physiological and temporal variation in the disposition of midazolam has been reported. In order to delineate the underlying mechanisms of these alterations, we infused in 5 healthy male volunteers for 26 hours midazolam at a rate of 0.025 mg/kg/h preceded by a bolus of 0.05 mg/kg. Thus, steady-state conditions were rapidly achieved. Plasma levels of midazolam were monitored on a 2-hourly basis during this period. In addition, the pharmacodynamic response to the new sedative/hypnotic benzodiazepine was characterised by a pencil tracking test, sedation index formed from visual analogue scales, and choice reaction time.In all subjects, small (4 to 16%) but clinically irrelevant fluctuations of steady-state plasma concentrations around 45 ng/ml were observed. During the night-time (11pm to 7am) plasma concentrations were slightly (p = 0.074) higher than during the daytime. Total plasma clearance varied from 563 to 823 ml/min. Plasma protein binding of midazolam was time independent.Since in only 1 of 5 subjects was a circadian rhythm observed, fluctuations in plasma midazolam concentrations under controlled and constant conditions are probably not of clinical significance.
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