The pharmacokinetics of midazolam in man
The pharmacokinetics of midazolam in man
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咪达唑仑在人体内的药代动力学
DOI：
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发表时间：
2004
影响因子：
2.9
通讯作者：
T. Brophy
中科院分区：
文献类型：
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作者：
Maree T. Smith;M. Eadie;T. Brophy
咪达唑仑是一种新的水溶性苯二氮卓类药物，给6名志愿者静脉注射5毫克，10毫克口服液和10毫克口服片剂。咪达唑仑血药浓度测定采用电子捕获气-液色谱分析。静注咪达唑仑5 mg后，受试者在1~2min内入睡，平均持续睡眠1.33h，口服咪达唑仑(溶液或片剂)后平均0.38h(0.25~0.55h)出现嗜睡，持续睡眠平均1.17h，10 mg溶液后达峰时间(0.37±0.45h)差异无统计学意义(t‘=2.04，df=10，p>)；0.05)从咪达唑仑10 mg剂量后血药浓度达到峰值开始(0.74±0.45h)。咪达唑仑在血浆中的终末半衰期(t1/2)为1.77±0.83h，3种剂型的平均终末半衰值差异无统计学意义。咪达唑仑5 mg静脉给药后的平均总清除量(CI)为0.383±0.094 L·kg−·h−1。4名受试者在0.011~8h尿液中的咪达唑仑剂量排泄量的百分比很小(4%~0.028%)。
SummaryMidazolam, a new water-soluble benzodiazepine, was administered as: i) 5 mg intravenously, ii) a 10-mg oral solution and iii) a 10-mg oral tablet, to six volunteers whose informed consent had been obtained. Midazolam plasma concentrations were measured using an electron-capture gas-liquid chromatographic assay. After 5-mg intravenous midazolam, subjects fell asleep within 1–2 min and continued to sleep for an average of 1.33 h. After oral midazolam intake (solution or tablets), drowsiness appeared after a average of 0.38 h (range 0.25–0.55 h) and sleep continued for an average of 1.17 h. The time to reach peak plasma midazolam concentration after the 10-mg solution dose (0.37±0.45 h) did not differe significantly (‘t’=2.04, df=10,p>0.05) from the time to reach peak plasma midazolam level after the 10-mg tablet dose (0.74±0.45 h). The terminal half-life, (t1/2), of midazolam in plasma was 1.77±0.83 h and there was no significant difference between the mean terminal half-life values obtained for the three midazolam formulations. The mean total clearance (Cl), of midazolam after 5-mg intravenous administration was 0.383±0.094 l·kg−1·h−1. The first pass effect, F, determined experimentally (0.36±0.09) indicated the substantial first pass metabolism of midazolam. The percentage of the midazolam dose excreted unchanged in urine in four subjects during the 0-8-h urine collection interval was very small (0.011%–0.028%).