Pollak P T
Department of Medicine, Victoria General Hospital, Dalhousie University, Halifax, Nova Scotia, Canada.
Ther Drug Monit. 1996 Dec;18(6):678-87. doi: 10.1097/00007691-199612000-00009.
Metronidazole is an important component of combination antimicrobial therapies used in the eradication of Helicobacter pylori, a recognized cause of gastritis and duodenal ulcer. Studies are needed to understand which pharmacokinetic factors determine the success of metronidazole therapy and what role drug monitoring plays. Such studies require a rapid, accurate assay for small volumes of sample, including gastric juice, over a 200-fold range of concentrations. Using an isocratic high-performance liquid chromatography (HPLC) method, with an 8-min run time and protein precipitation of samples, metronidazole could be measured reliably to as low as 0.5 mg/L in 100 microliters samples of serum, gastric juice, or saliva. Standard curves for serum and gastric juice were linear between 0.5 and 50 mg/L. Within-day coefficients of variation (CVs) (n = 5 at six concentrations) ranged from 1.1 to 4.8% over this range and the between-day CV (n = 7 days) was 5.8%. Neither omeprazole nor common gastroenteric and cardiac medications interfered with this assay. A pilot study, done in four healthy volunteers given intravenous metronidazole 500 mg before and after 7 days of omeprazole therapy, found metronidazole to be present in higher concentrations in gastric juice and saliva than in serum 2 h after intravenous administration. The range and accuracy of the assay proved to be suitable for carrying out pharmacokinetic studies at clinically used doses of the drug.
甲硝唑是用于根除幽门螺杆菌的联合抗菌疗法的重要组成部分，幽门螺杆菌是胃炎和十二指肠溃疡的公认病因。需要开展研究以了解哪些药代动力学因素决定甲硝唑治疗的成功与否以及药物监测发挥何种作用。此类研究需要一种能够对小体积样本（包括胃液）在200倍浓度范围内进行快速、准确检测的方法。采用等度高效液相色谱（HPLC）法，运行时间为8分钟且对样本进行蛋白沉淀，在100微升血清、胃液或唾液样本中，甲硝唑的可靠检测下限可达0.5毫克/升。血清和胃液的标准曲线在0.5至50毫克/升之间呈线性。在此浓度范围内，日内变异系数（CVs）（六个浓度下n = 5）在1.1%至4.8%之间，日间CV（n = 7天）为5.8%。奥美拉唑以及常见的胃肠和心脏药物均不干扰该检测。一项初步研究在四名健康志愿者身上开展，在奥美拉唑治疗7天前后静脉注射500毫克甲硝唑，结果发现静脉给药2小时后，胃液和唾液中甲硝唑的浓度高于血清中的浓度。该检测的范围和准确性证明适用于在临床使用剂量下开展该药物的药代动力学研究。
