Lau A H, Evans R, Chang C W, Seligsohn R
College of Pharmacy, University of Illinois, Chicago 60612.
Antimicrob Agents Chemother. 1987 Nov;31(11):1662-4. doi: 10.1128/AAC.31.11.1662.
The pharmacokinetics of metronidazole was evaluated in eight patients with alcoholic liver disease. Metronidazole (7.5 mg/kg) was administered to each patient intravenously. Serial blood samples were obtained after the dose. Serum metronidazole concentrations were determined by high-performance liquid chromatography. The following pharmacokinetic parameters (mean +/- standard deviations) were obtained: half-life, 18.31 +/- 6.06 h; elimination rate constant, 0.042 +/- 0.013 h-1; volume of distribution, 0.77 +/- 0.16 liters/kg; and total body clearance, 0.51 +/- 0.11 ml/min per kg. Compared with subjects with normal liver function, patients with liver disease showed a reduction in drug elimination rate and total body clearance. The half-life of metronizadole in serum and volume of distribution were increased. Large variations of these parameters were also observed among the patients. On the basis of these observations, a reduced dose of metronidazole should be given to patients with alcoholic liver disease to avoid accumulation of metronidazole and its metabolites. Monitoring of drug concentration in serum may also be necessary to optimize therapy.
对8例酒精性肝病患者的甲硝唑药代动力学进行了评估。给每位患者静脉注射甲硝唑（7.5mg/kg）。给药后采集系列血样。采用高效液相色谱法测定血清甲硝唑浓度。获得以下药代动力学参数（平均值±标准差）：半衰期，18.31±6.06小时；消除速率常数，0.042±0.013 h⁻¹；分布容积，0.77±0.16升/千克；全身清除率，0.51±0.11毫升/分钟/千克。与肝功能正常的受试者相比，肝病患者的药物消除速率和全身清除率降低。血清中甲硝唑的半衰期和分布容积增加。在患者中也观察到这些参数的较大差异。基于这些观察结果，应给予酒精性肝病患者较低剂量的甲硝唑，以避免甲硝唑及其代谢产物的蓄积。为优化治疗，监测血清药物浓度可能也是必要的。
