Nakashima M, Kanamaru M, Uematsu T, Takiguchi A, Mizuno A, Itaya T, Kawahara F, Ooie T, Saito S, Uchida H
Department of Pharmacology, Hamamatsu University School of Medicine, Shizuoka, Japan.
J Antimicrob Chemother. 1988 Oct;22 Suppl D:133-44. doi: 10.1093/jac/22.supplement_d.133.
The tolerance and pharmacokinetics of fleroxacin were studied in healthy male adult volunteers. The peak serum concentrations of unchanged fleroxacin were about 1.5, 3 and 5 mg/l at 1-2 h after single oral doses of 100, 200 and 400 mg, respectively. The apparent serum elimination half-life was about 10 h, independent of the dose. Fleroxacin, demethyl fleroxacin and fleroxacin N-oxide excreted in urine over 3 days accounted for about 75%, 5% and 5%, respectively, of the doses. The urine concentrations of unchanged drug were dose-related; the mean concentrations, sustained over 24 h, were about 50, 100 and 150 mg/l after 100, 200 and 400 mg doses, respectively. Food intake did not significantly influence the serum concentration and urinary excretion. Steady state serum concentrations were achieved from day 3 onwards by repeated doses of twice-a-day dosage regimen and were 2-4 and 5-9 mg/l after 200 and 400 mg bid, respectively. The mean concentrations of unchanged drug in urine were about 200 and 300 mg/l at the respective dosages. The pattern of urinary metabolites was not changed by repeated doses and 90% of repeat doses was recovered in urine, including metabolites. The serum protein binding of fleroxacin was 32%. The saliva concentration was 40% of the total serum concentration or 60% of the free serum concentration. The faecal recovery over 3 days was 3% of the dose following a single 200 mg dose after a meal. The unchanged drug concentrations in faeces during 400 mg repeated dosing were 100-150 mg/kg. No severe dose-related side-effects were observed during the study.
在健康成年男性志愿者中研究了氟罗沙星的耐受性和药代动力学。单次口服100、200和400mg后，1 - 2小时未变化的氟罗沙星的血清峰值浓度分别约为1.5、3和5mg/L。表观血清消除半衰期约为10小时，与剂量无关。3天内尿中排出的氟罗沙星、去甲基氟罗沙星和氟罗沙星N - 氧化物分别约占给药剂量的75%、5%和5%。未变化药物的尿浓度与剂量相关；100、200和400mg剂量后，24小时持续的平均浓度分别约为50、100和150mg/L。食物摄入对血清浓度和尿排泄无显著影响。通过每日两次重复给药方案，从第3天开始达到稳态血清浓度，200mg bid和400mg bid后分别为2 - 4mg/L和5 - 9mg/L。各剂量下尿中未变化药物的平均浓度分别约为200和300mg/L。重复给药未改变尿代谢产物的模式，90%的重复剂量在尿中回收，包括代谢产物。氟罗沙星的血清蛋白结合率为32%。唾液浓度为总血清浓度的40%或游离血清浓度的60%。餐后单次服用200mg剂量后，3天内粪便回收率为给药剂量的3%。400mg重复给药期间粪便中未变化药物浓度为100 - 150mg/kg。研究期间未观察到严重的剂量相关副作用。
