Penzak Scott R, Busse Kristin H, Robertson Sarah M, Formentini Elizabeth, Alfaro Raul M, Davey Richard T
Clinical Pharmacokinetics Research Laboratory, National Institutes of Health, Clinical Center Pharmacy Department, Bldg 10, Room 1N 257, Bethesda, MD 20892, USA.
J Clin Pharmacol. 2008 Jun;48(6):671-80. doi: 10.1177/0091270008317305. Epub 2008 Apr 16.
Midazolam is a common probe used to predict CYP3A activity, but multiple blood samples are necessary to determine midazolam's area under the concentration-time curve (AUC). As such, single sampling strategies have been examined. The purpose of this study was to assess the ability of single midazolam concentrations to predict midazolam AUC in the presence and absence of CYP3A modulation by Ginkgo biloba extract (GBE). Subjects received oral midazolam 8 mg before and after 28 days of GBE administration. Postdose blood samples were collected during both study periods and midazolam AUC determined. Linear regression was used to generate measures of predictive performance for each midazolam concentration. The geometric mean ratio (90% confidence intervals) of midazolam AUC(0-infinity) post-GBE/AUC(0-infinity) pre-GBE was 0.66 (0.49-0.84) (P = .03). Before and after GBE administration, optimal midazolam sampling times were identified at 3.5 to 5 hours and 2 to 3 hours, respectively. Single midazolam concentrations between 2 and 5 hours correctly predicted the reduction in midazolam AUC following GBE exposure, but confidence intervals were generally wide. Intersubject variability in CYP3A activity (either inherent or from drug administration) alters the prediction of optimal midazolam sampling times; therefore, midazolam AUC is preferred for assessing CYP3A activity in drug-drug interaction studies.
咪达唑仑是一种常用于预测CYP3A活性的探针，但需要采集多份血样来测定咪达唑仑的浓度-时间曲线下面积（AUC）。因此，人们对单次采样策略进行了研究。本研究的目的是评估在银杏叶提取物（GBE）存在或不存在的情况下，单次咪达唑仑浓度预测咪达唑仑AUC的能力。受试者在服用GBE 28天前后分别口服8 mg咪达唑仑。在两个研究期间均采集给药后的血样并测定咪达唑仑的AUC。采用线性回归生成每个咪达唑仑浓度的预测性能指标。GBE给药后咪达唑仑AUC(0-无穷大)/给药前咪达唑仑AUC(0-无穷大)的几何平均比值（90%置信区间）为0.66（0.49 - 0.84）（P = 0.03）。在服用GBE前后，分别确定最佳咪达唑仑采样时间为3.5至5小时和2至3小时。2至5小时之间的单次咪达唑仑浓度正确预测了GBE暴露后咪达唑仑AUC的降低，但置信区间通常较宽。CYP3A活性的个体间差异（无论是内在的还是药物给药引起的）会改变最佳咪达唑仑采样时间的预测；因此，在药物相互作用研究中，评估CYP3A活性时首选咪达唑仑AUC。
