Taburet A M, Devillers A, Thomare P, Fillastre J P, Veyssier P, Singlas E
Clinical Pharmacy, Hôpital Bicètre, Paris, France.
Clin Pharmacokinet. 1990 Jul;19(1):80-8. doi: 10.2165/00003088-199019010-00006.
The pharmacokinetics of fleroxacin and its main metabolites, N-demethyl-fleroxacin and N-oxide-fleroxacin, were studied in 12 elderly patients aged 63 to 88 years. Plasma and urine samples collected at different times after drug administration were analysed by a specific reverse phase high performance liquid chromatography (HPLC) method. The peak plasma concentration (Cmax) of fleroxacin was 15.6 +/- 1.6 mg/L, time to Cmax (tmax) was about 3h, elimination half-life (t1/2) was 16 +/- 1h and the percentage of unchanged fleroxacin excreted in urine was 39 +/- 3% of the dose. The plasma concentrations of metabolites were very low and accounted for no more than 4% of the concentration of unchanged fleroxacin. Plasma parameters were mainly correlated with age and weight; urinary parameters were correlated with creatinine clearance. Compared with results in younger normal patients, no significant change in the t1/2 of fleroxacin or metabolites was observed. Assuming that the bioavailability (f) is complete, the apparent volume of distribution (Vd/f) was lower in elderly (0.9 +/- 0.1 L/kg) than in younger patients (1.3 +/- 0.1 L/kg) and a 2-fold decrease in apparent total clearance (CL/f) was noted (2.58 +/- 0.42 vs 4.86 +/- 0.72 L/h); plasma concentrations were consequently higher in elderly patients. Compared with patients with renal failure, the pharmacokinetics of fleroxacin and metabolites in the elderly were similar to those of patients with mild to moderate renal insufficiency. On the basis of the findings of this single dose study, no major dosage adjustments are needed for patients of this age range except for those with creatinine clearance less than 30 ml/min.
对12名年龄在63至88岁的老年患者进行了氟罗沙星及其主要代谢产物N - 去甲基氟罗沙星和N - 氧化氟罗沙星的药代动力学研究。给药后不同时间采集的血浆和尿液样本采用特定的反相高效液相色谱（HPLC）法进行分析。氟罗沙星的血浆峰浓度（Cmax）为15.6±1.6mg/L，达峰时间（tmax）约为3小时，消除半衰期（t1/2）为16±1小时，尿液中排泄的未变化氟罗沙星占给药剂量的39±3%。代谢产物的血浆浓度非常低，不超过未变化氟罗沙星浓度的4%。血浆参数主要与年龄和体重相关；尿液参数与肌酐清除率相关。与年轻正常患者的结果相比，未观察到氟罗沙星或其代谢产物的t1/2有显著变化。假设生物利用度（f）完全，老年患者的表观分布容积（Vd/f）低于年轻患者（0.9±0.1L/kg vs 1.3±0.1L/kg），表观总清除率（CL/f）降低了2倍（2.58±0.42 vs 4.86±0.72L/h）；因此老年患者的血浆浓度更高。与肾衰竭患者相比，老年患者中氟罗沙星及其代谢产物的药代动力学与轻度至中度肾功能不全患者相似。基于该单剂量研究的结果，除肌酐清除率低于30ml/min的患者外，该年龄范围的患者无需进行重大剂量调整。
