Schneider M U, Riemann J F, Laudage G
Chemotherapy. 1984;30(6):345-52. doi: 10.1159/000238292.
Serum concentrations of metronidazole and its main metabolite [1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole] have been determined by high performance liquid chromatography in sera of 10 patients with histologically confirmed ileocolitis Crohn, 7 presenting with highly active disease and pathologically increased Crohn's disease activity index (CDAI) and 3 with secreting fistulas but normal CDAI. Metronidazole serum concentrations showed dose-dependent peak characteristics and ranged between 10.62 +/- 0.95 and 24.88 +/- 3.63 micrograms/ml for a metronidazole intake of 1,000 mg/day and between 5.04 +/- 1.13 and 9.21 +/- 1.00 micrograms/ml for a daily intake of 400 mg, whereas its metabolite leveled at constant serum concentrations up to 24 h after onset of therapy, with 7.50 +/- 1.40 micrograms/ml for a metronidazole intake of 1,000 mg/day and 3.20 +/- 0.60 microgram/ml for an intake of 400 mg/day. Considering the known minimum inhibitory concentration of metronidazole for anaerobic bacteria involved in Crohn's disease, this work has shown 400 mg metronidazole to be the minimum daily dosage. Correlation analysis, although limited by the small number of patients investigated so far, indicated a possible positive correlation between metronidazole serum concentrations and disease activity (CDAI, r = 0.480) and therapeutic efficacy (delta CDAI, r = 0.430) in Crohn's disease.
采用高效液相色谱法测定了10例经组织学确诊为克罗恩回结肠炎患者血清中甲硝唑及其主要代谢产物[1-(2-羟乙基)-2-羟甲基-5-硝基咪唑]的浓度。其中7例患者病情高度活跃，克罗恩病活动指数（CDAI）病理值升高；3例患者有分泌性瘘管，但CDAI正常。甲硝唑血清浓度呈现剂量依赖性峰值特征，甲硝唑摄入量为1000mg/天时，浓度范围在10.62±0.95至24.88±3.63μg/ml之间；每日摄入量为400mg时，浓度范围在5.04±1.13至9.21±1.00μg/ml之间。而其代谢产物在治疗开始后24小时内血清浓度保持恒定，甲硝唑摄入量为1000mg/天时为7.50±1.40μg/ml，摄入量为400mg/天时为3.20±0.60μg/ml。考虑到已知甲硝唑对参与克罗恩病的厌氧菌的最低抑菌浓度，这项研究表明400mg甲硝唑是每日最低剂量。尽管目前受调查患者数量有限，但相关性分析表明，克罗恩病患者血清中甲硝唑浓度与疾病活动度（CDAI，r = 0.480）和治疗效果（ΔCDAI，r = 0.430）之间可能存在正相关。
