Somogyi A A, Kong C B, Gurr F W, Sabto J, Spicer W J, McLean A J
J Antimicrob Chemother. 1984 Feb;13(2):183-9. doi: 10.1093/jac/13.2.183.
The pharmacokinetics and metabolism of intravenous metronidazole were studied in six patients with acute renal failure. In two of the patients a single dose (500 mg) of metronidazole was administered, whereas in four patients the steady-state pharmacokinetics were studied after four days therapy of 500 mg twice daily. Plasma concentrations of metronidazole and its hydroxy and acetic acid metabolites were measured by a specific and sensitive HPLC method. The volume of distribution was 0.65 +/- 0.13 l/kg (mean +/- S.D.), elimination half-life was 9.9 +/- 2.5 h and total plasma clearance was 55.5 +/- 17.7 ml/min. Renal clearance was almost non-existent (1.4 +/- 1.4 ml/min), whereas non-renal clearance was 54.0 +/- 18.2 ml/min. Steady-state plasma concentrations of metronidazole were 15.3 +/- 3.8 mg/l, the hydroxy metabolite were 17.4 +/- 2.0 mg/l and the acetic acid metabolite were 1.2 +/- 0.8 mg/l. In the patients studied, a dosing regimen of 500 mg twice daily resulted in therapeutically adequate blood levels of metronidazole.
对6例急性肾衰竭患者进行了静脉注射甲硝唑的药代动力学和代谢研究。其中2例患者给予单次剂量（500mg）的甲硝唑，而另外4例患者在每日2次、每次500mg治疗4天后研究其稳态药代动力学。采用特异性灵敏的高效液相色谱法测定血浆中甲硝唑及其羟基和乙酸代谢物的浓度。分布容积为0.65±0.13l/kg（均值±标准差），消除半衰期为9.9±2.5小时，血浆总清除率为55.5±17.7ml/min。肾清除率几乎不存在（1.4±1.4ml/min），而非肾清除率为54.0±18.2ml/min。甲硝唑的稳态血浆浓度为15.3±3.8mg/l，羟基代谢物为17.4±2.0mg/l，乙酸代谢物为1.2±0.8mg/l。在所研究的患者中，每日2次、每次500mg的给药方案可使甲硝唑的血药水平达到治疗所需浓度。
