Bornemann L D, Crews T, Chen S S, Twardak S, Patel I H
J Clin Pharmacol. 1986 Jan;26(1):55-9. doi: 10.1002/j.1552-4604.1986.tb02903.x.
The influence of food on the absorption of midazolam, a new benzodiazepine derivative, was investigated in 18 healthy volunteers in a four-way, randomized, crossover study with a one-week washout period between treatments. Single 15-mg oral doses of midazolam were administered one hour before, with, and one hour after a standard meal as well as under fasting conditions (control). Following serial blood sampling over the next 24-hour period, midazolam plasma concentrations were determined by gas chromatography and mass spectrometry for pharmacokinetic evaluation. The maximum plasma concentration (Cmax), time of maximum concentration (tmax), lag time prior to absorption (tlag), area under the plasma concentration-time curve (AUC), and elimination rate constant of midazolam and 1-hydroxymethylmidazolam were determined. Significant changes in these parameters were not found when midazolam was taken one hour before or with a meal as compared with the control condition. Significant changes in the Cmax, tmax, and AUC parameters for both midazolam and its metabolite were seen when midazolam was ingested one hour after a meal: There was a delayed and reduced rate of absorption as well as a small reduction in the extent of absorption. Thus, ingestion of midazolam within one hour after a meal may result in a delay in the onset of the pharmacologic effect. These changes may be of some clinical significance in that they may potentially delay the onset of sleep.
在一项有18名健康志愿者参与的四路随机交叉研究中，考察了食物对一种新型苯二氮䓬衍生物咪达唑仑吸收的影响，各治疗组之间有一周的洗脱期。分别在标准餐进食前1小时、进食时、进食后1小时以及空腹条件下（对照）给予单次15mg口服咪达唑仑。在接下来的24小时内进行系列采血后，采用气相色谱和质谱法测定咪达唑仑血浆浓度以进行药代动力学评价。测定了咪达唑仑和1-羟甲基咪达唑仑的最大血浆浓度（Cmax）、达峰时间（tmax）、吸收前的延迟时间（tlag）、血浆浓度-时间曲线下面积（AUC）以及消除速率常数。与对照条件相比，在进食前1小时或进食时服用咪达唑仑时，这些参数未发现显著变化。当在进食后1小时服用咪达唑仑时，咪达唑仑及其代谢产物的Cmax、tmax和AUC参数均出现显著变化：吸收速率延迟且降低，吸收程度也略有降低。因此，进食后1小时内服用咪达唑仑可能会导致药理作用起效延迟。这些变化可能具有一定的临床意义，因为它们可能会潜在地延迟入睡时间。
