Eradiri O, Jamali F, Thomson A B
Biopharm Drug Dispos. 1987 May-Jun;8(3):249-59. doi: 10.1002/bdd.2510080306.
The pharmacokinetics of metronidazole (MTZ) were studied in six Crohn's disease patients after multiple oral daily doses of 250, 500, 750, and 1000 mg day-1. Pharmacokinetic indices were found to be independent of the dose administered. The half-life, volume of distribution and oral clearance of metronidazole were 9.5 +/- 2.1 h, 0.732 +/- 0.094 l kg-1 and 0.921 +/- 0.175 (ml min-1) kg-1 (mean +/- SD), respectively. A strong linear correlation (r = 0.95) was found between the volume of distribution of MTZ and the patients' total body weight. The percentage of dose of metronidazole excreted in urine as the intact drug and metabolites as well as glucuronic acid conjugates ranged from 34.7 +/- 7.4 to 58.9 +/- 5.2. Both plasma and urine data exhibited very large inter-patient variations. However, intra-patient variations were negligible. Strong positive linear correlations were observed between the dose and the areas under the plasma concentration versus time curves, peak plasma concentrations as well as cumulative urinary excretion of the drug and its metabolites. It is concluded that in Crohn's disease, the pharmacokinetics of MTZ and its metabolites are linear and that the drug concentrations are dependent on the total body weight.
在6例克罗恩病患者中，研究了每日多次口服250、500、750和1000 mg甲硝唑（MTZ）后的药代动力学。发现药代动力学指标与给药剂量无关。甲硝唑的半衰期、分布容积和口服清除率分别为9.5±2.1小时、0.732±0.094 l·kg⁻¹和0.921±0.175（ml·min⁻¹）·kg⁻¹（平均值±标准差）。MTZ的分布容积与患者总体重之间存在强线性相关性（r = 0.95）。以原形药物、代谢产物以及葡萄糖醛酸结合物形式经尿液排泄的甲硝唑剂量百分比范围为34.7±7.4至58.9±5.2。血浆和尿液数据均显示患者间差异非常大。然而，患者内差异可忽略不计。观察到剂量与血浆浓度-时间曲线下面积、血浆峰浓度以及药物及其代谢产物的累积尿排泄量之间存在强正线性相关性。结论是，在克罗恩病中，MTZ及其代谢产物的药代动力学呈线性，且药物浓度取决于总体重。
