Pharmacokinetics and biliary concentrations of fleroxacin in cholecystectomized patients
Pharmacokinetics and biliary concentrations of fleroxacin in cholecystectomized patients
复制标题
胆囊切除患者中氟罗沙星的药代动力学和胆汁浓度
DOI：
10.1128/aac.34.12.2375
复制
发表时间：
1990
影响因子：
4.9
通讯作者：
E. Weidekamm
中科院分区：
文献类型：
--
作者：
W. Hayton;V. Vlahov;N. Bacracheva;I. Viachki;R. Portmann;G. Muirhead;K. Stoeckel;E. Weidekamm
胆道感染患者接受800 mg氟罗沙星口服，每日一次，连续5天;胆囊切除术在第3天进行。从第5次给药当天开始，连续采集血液和T型引流管胆汁样本72 h，并采集尿液96 h。8.3 h时血浆中的平均（+/-标准差）峰浓度为8.2 +/-4.0 mg/L。调和平均消除半衰期为10.5 h，与健康志愿者报告的结果相当。这种增加是由于肾清除率降低（平均值[+/-标准差]，38 +/-22 ml/min），因为患者的分布容积（1.4 +/-0.7 L/kg）与健康受试者报告的分布容积无差异。T型引流管胆汁中的最大浓度较高（中位数为22.1 mg/L），超过血浆中测得的浓度2 - 3倍;胆汁曲线下面积除以血浆曲线下面积的个体比值范围为1.3 - 9.9。如在健康志愿者中观察到的，氟罗沙星消除的主要途径是通过肾脏。然而，0 - 24小时尿液中消除的剂量5的分数降低，尿液中作为N-去甲基和N-氧化物代谢产物的剂量分数升高。在本研究中使用的剂量方案下，血浆和胆汁中大多数引起胆道感染的病原体的MIC超过24小时。
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.