Hayton W L, Vlahov V, Bacracheva N, Viachki I, Portmann R, Muirhead G, Stoeckel K, Weidekamm E
College of Pharmacy, Washington State University, Pullman 99164-6510.
Antimicrob Agents Chemother. 1990 Dec;34(12):2375-80. doi: 10.1128/AAC.34.12.2375.
Patients with biliary tract infections received 800 mg of fleroxacin orally once daily on five consecutive days; cholecystectomy was on day 3. Starting on the day when dose 5 was administered, serial blood and T-drain bile samples were taken for 72 h and urine was collected for 96 h. The mean (+/- the standard deviation) peak concentration in plasma was 8.2 +/- 4.0 mg/liter at 8.3 h. The harmonic mean elimination half-life was 10.5 h, which is comparable to that reported for healthy volunteers. This increase resulted from reduced renal clearance (mean [+/- standard deviation], 38 +/- 22 ml/min), as the volume of distribution in the patients (1.4 +/- 0.7 liter/kg) did not differ from that reported for healthy subjects. Maximum concentrations in T-drain bile were high (median, 22.1 mg/liter) and exceeded those measured in plasma by a factor of 2 to 3; the individual ratios of the area under the curve for bile divided by that for plasma ranged from 1.3 to 9.9. As observed in healthy volunteers, the major pathway for elimination of fleroxacin was via the kidneys. The fraction of dose 5 eliminated in the 0- to 24-h urine was reduced, however, and the fraction of the dose in the urine as the N-demethyl and N-oxide metabolites was elevated. At the dose regimen used in this study, the MICs for most pathogens that cause biliary tract infections were surpassed in plasma and bile for more than 24 h.
胆道感染患者连续5天每天口服800毫克氟罗沙星；在第3天进行胆囊切除术。从给予第5剂药物的当天开始，连续72小时采集系列血液和T形引流胆汁样本，并收集96小时尿液。血浆中平均（±标准差）峰浓度在8.3小时时为8.2±4.0毫克/升。谐波平均消除半衰期为10.5小时，与健康志愿者报告的半衰期相当。这种增加是由于肾清除率降低（平均[±标准差]，38±22毫升/分钟），因为患者的分布容积（1.4±0.7升/千克）与健康受试者报告的分布容积没有差异。T形引流胆汁中的最大浓度很高（中位数为22.1毫克/升），超过血浆中测得浓度的2至3倍；胆汁曲线下面积与血浆曲线下面积的个体比值范围为1.3至9.9。正如在健康志愿者中观察到的那样，氟罗沙星的主要消除途径是通过肾脏。然而，第5剂药物在0至24小时尿液中消除的比例降低，尿液中作为N-去甲基和N-氧化物代谢物的剂量比例升高。在本研究使用的给药方案下，血浆和胆汁中超过24小时超过了大多数引起胆道感染病原体的最低抑菌浓度。
