Ljungberg B, Nilsson-Ehle I, Ursing B
J Antimicrob Chemother. 1984 Sep;14(3):275-83. doi: 10.1093/jac/14.3.275.
Single and multiple dose pharmacokinetics of metronidazole and its two major metabolites were studied in ten patients. Patients with hepatic insufficiency had longer average serum half-life of metronidazole (11.2 h) than individuals with normal liver and kidney function (5.9 h) or isolated moderate renal impairment (6.5 h). Patients with hepatic disorder presented larger areas under the serum concentration curve, lower serum clearances and a tendency to more rapidly rising trough values of metronidazole. In patients with renal insufficiency trough values of the hydroxy metabolite seemed to rise faster and serum half-life was prolonged. The acetic acid metabolite was detected in serum of all patients with renal dysfunction but only in half of those with normal renal function and then at lower levels. A reduced 24-h total urinary recovery of metronidazole among patients with renal disorder was explained by a decreased excretion of hydroxy metabolite. The kinetics of metronidazole itself seem not to be influenced by renal impairment while the elimination rate of metabolites is reduced. The decreased clearance of the drug in patients with hepatic dysfunction makes a dose reduction in this patient group advisable.
在10名患者中研究了甲硝唑及其两种主要代谢物的单剂量和多剂量药代动力学。肝功能不全患者的甲硝唑平均血清半衰期（11.2小时）比肝肾功能正常的个体（5.9小时）或单纯中度肾功能损害患者（6.5小时）更长。肝脏疾病患者的血清浓度曲线下面积更大，血清清除率更低，且甲硝唑谷值有更快上升的趋势。在肾功能不全患者中，羟基代谢物的谷值似乎上升得更快，血清半衰期延长。所有肾功能不全患者的血清中均检测到乙酸代谢物，但肾功能正常患者中只有一半检测到，且含量较低。肾功能障碍患者甲硝唑24小时总尿回收率降低是由于羟基代谢物排泄减少所致。甲硝唑本身的动力学似乎不受肾功能损害的影响，而代谢物的消除率降低。肝功能不全患者药物清除率降低，因此建议该患者组减少剂量。
