Weidekamm E, Portmann R, Partos C, Dell D
Department of Clinical Research, F. Hoffmann-La Roche, Basel, Switzerland.
J Antimicrob Chemother. 1988 Oct;22 Suppl D:145-54. doi: 10.1093/jac/22.supplement_d.145.
Pharmacokinetics of fleroxacin following single and multiple dosing were studied in healthy male volunteers. The characteristics of this new trifluorinated quinolone are the long elimination half-life of approximately 10 h and the high plasma concentrations, which exceed 2 mg/l after an oral dose of 200 mg. These two parameters are a prerequisite for a once daily dosage regimen. A good linear relationship (r = 0.998) was found between administered doses (100-2500 mg) and resulting AUC values. The volume of distribution (Vss) exceeded 1 l/kg and reflects the good tissue penetration. Renal clearance of unbound drug was 104 ml/min and within three days 56% of the dose could be recovered from urine as unchanged drug. Multiple dosing of 800 or 1200 mg fleroxacin once daily over ten days resulted in an accumulation of the drug in the plasma by a factor of 1.4. This value is in agreement with the theoretically predicted accumulation and thus non-linear, time-dependent pharmacokinetics can be excluded. The administered tablets were completely bioavailable (F = 1.0) and a significant first pass metabolism can therefore be excluded.
在健康男性志愿者中研究了单次和多次给药后氟罗沙星的药代动力学。这种新型三氟喹诺酮的特点是消除半衰期约为10小时，血浆浓度高，口服200毫克后超过2毫克/升。这两个参数是每日一次给药方案的先决条件。给药剂量（100 - 2500毫克）与所得AUC值之间发现良好的线性关系（r = 0.998）。分布容积（Vss）超过1升/千克，反映出良好的组织穿透力。游离药物的肾清除率为104毫升/分钟，三天内56%的剂量可作为原形药物从尿液中回收。连续十天每天一次给予800或1200毫克氟罗沙星导致药物在血浆中蓄积1.4倍。该值与理论预测的蓄积一致，因此可以排除非线性、时间依赖性药代动力学。所给药片完全生物利用（F = 1.0），因此可以排除显著的首过代谢。
