Cheng F C, Ho Y F, Hung L C, Chen C F, Tsai T H
Department of Medical Research, Taichung Veterans General Hospital, Taiwan.
J Chromatogr A. 2002 Mar 8;949(1-2):35-42. doi: 10.1016/s0021-9673(01)01225-0.
The disposition and biliary excretion of omeprazole was investigated following i.v. administration to rats at 10 mg/kg. We used a microdialysis technique coupled to a validated microbore HPLC system to monitor the levels of protein-unbound omeprazole in rat blood, brain and bile, constructing the relationship of the time course of the presence of omeprazole. Microdialysis probes were simultaneously inserted into the jugular vein toward right atrium, the brain striatum and the bile duct of the male Sprague-Dawley rats for biological fluid sampling after the administration of omeprazole (10 mg/kg) through the femoral vein. The concentration-response relationship from the present method indicated linearity (r2>0.995) over a concentration range of 0.01-50 microg/ml for omeprazole. Intra-assay and inter-assay precision and accuracy of omeprazole fell well within the predefined limits of acceptability. Following omeprazole administration, the blood-to-brain coefficient of distribution was 0.15, which was calculated as the area under the concentration versus time curve (AUC) in the brain divided by the AUC in blood (k=AUCbrain/AUCblood). The blood-to-bile coefficient of distribution (k=AUCbile/AUCblood) was 0.58. The decline of unbound omeprazole in the brain striatum, blood and bile fluid suggests that there was rapid exchange and equilibration between the compartments of the peripheral and central nervous systems. In addition, the results indicated that omeprazole was able to penetrate the blood-brain barrier and undergo hepatobiliary excretion.
在以10mg/kg的剂量对大鼠进行静脉注射后，研究了奥美拉唑的处置和胆汁排泄情况。我们使用了一种与经过验证的微径高效液相色谱系统相结合的微透析技术，来监测大鼠血液、大脑和胆汁中未与蛋白质结合的奥美拉唑水平，构建奥美拉唑存在的时间过程关系。在通过股静脉给雄性Sprague-Dawley大鼠注射奥美拉唑（10mg/kg）后，将微透析探针同时插入颈静脉朝向右心房、脑纹状体和胆管，以采集生物体液样本。本方法的浓度-反应关系表明，在0.01-50μg/ml的奥美拉唑浓度范围内呈线性（r2>0.995）。奥美拉唑的批内和批间精密度及准确度均在预先定义的可接受限度内。给予奥美拉唑后，血脑分布系数为0.15，计算方法为脑内浓度-时间曲线下面积（AUC）除以血液中的AUC（k=AUCbrain/AUCblood）。血胆汁分布系数（k=AUCbile/AUCblood）为0.58。脑纹状体、血液和胆汁液中未结合的奥美拉唑的下降表明，外周和中枢神经系统各隔室之间存在快速交换和平衡。此外，结果表明奥美拉唑能够穿透血脑屏障并进行肝胆排泄。
