AIMS:To examine diurnal variation in biliary excretion of flomoxef. METHODS:Flomoxef (1 g) was injected intravenously in eight patients with percutaneous transhepatic cholangiography with drainage at 09.00 h and 21.00 h by a cross-over design with a 36 h washout period. Drained biliary fluid was collected for 6 h after each dosing. These patients still had mild to moderate hepatic dysfunction. RESULTS:Bile flow and bile acid excretion for 6 h after dosing did not differ significantly between the 09.00 h and 21.00 h treatments. The maximum concentration of biliary flomoxef was significantly greater and its total excretion for 6 h tended to be greater after the 21.00 h dose [maximum concentration (microg ml(-1)): 34.2 +/- 29.9 (09.00 h dose) vs 43.5 +/- 28.3 (21.00 h dose) (95% confidence interval for difference: 2.6 approximately 15.9, P = 0.013); total excretion (mg 6 h(-1)): 1.4 +/- 1.3 (09.00 h dose) vs 1.6 +/- 1.2 (21.00 h dose) (95% confidence interval for difference: -26.8, 313.7, P = 0.087)]. The period that biliary flomoxef remained above the minimal inhibitory concentration did not differ significantly between the two treatment times. CONCLUSIONS:These results suggest that biliary excretion of flomoxef shows diurnal variation. However, as the difference was relatively small, flomoxef could be given at any time of day without any dosage adjustments.

译文

目的:研究氟莫昔夫的胆汁排泄量的日变化。
方法:对8例经皮经肝穿刺胆道造影术的患者静脉注射氟洛昔芬(1 g),并在09.00 h和21.00 h采用交叉设计,冲洗时间为36 h,进行引流。每次给药后6小时收集排出的胆汁。这些患者仍患有轻度至中度肝功能障碍。
结果:给药后6 h的胆汁流量和胆汁酸排泄在09.00 h和21.00 h处理之间无显着差异。在21.00 h剂量后,胆汁氟莫昔芬的最大浓度明显更高,其总排泄量6 h趋于更大[最大浓度(microg ml(-1)):34.2 /-29.9(09.00 h剂量)vs 43.5 /- 28.3(21.00小时剂量)(差异的95%置信区间:2.6约为15.9,P = 0.013);总排泄量(mg 6 h(-1)):1.4 /-1.3(09.00 h剂量)vs 1.6 /-1.2(21.00 h剂量)(差异的95%置信区间:-26.8,313.7,P = 0.087)]。在两个治疗时间之间,氟莫昔夫保持高于最低抑菌浓度的时间段无显着差异。
结论:这些结果表明氟莫昔夫的胆汁排泄表现为昼夜变化。但是,由于差异相对较小,可以在一天中的任何时间使用氟莫昔芬,而无需进行任何剂量调整。

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