Single- and multiple-dose pharmacokinetics of fleroxacin, a trifluorinated quinolone, in humans
- 1 December 1987
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 31 (12) , 1909-1914
- https://doi.org/10.1128/aac.31.12.1909
Abstract
Fleroxacin (Ro 23-6240; AM-833) is a new trifluorinated quinolone exhibiting high activity against a broad spectrum of gram-negative and gram-positive bacteria. Healthy male volunteers received, according to a randomized scheme, oral doses of 200, 400, or 800 mg of fleroxacin in tablet form, an intravenous infusion of 100 mg, or 400 mg of fleroxacin orally together with 1,000 mg of probenecid. Fleroxacin is characterized pharmacokinetically by a long elimination half-life (9 to 10 h) and high concentrations in plasma (e.g., maximum concentration of 2.3 micrograms/ml after an oral dose of 200 mg). The volume of distribution clearly exceeds 1 liter/kg and suggests a good tissue penetration. Within 60 h, the cumulative urinary recovery of unchanged drug amounted to 50 to 60% of the dose. The renal clearance of unbound drug was 137 ml/min, and probenecid had no significant effect on renal elimination. A good linear correlation (r = 0.999) was found between doses from 100 to 800 mg and the resulting values of area under the concentration-time curve. The absolute bioavailability of the administered tablet was practically 100%. During oral multiple dosing of 800 or 1,200 mg of fleroxacin once a day over 10 consecutive days, the accumulation of the drug in plasma was close to the theoretically predicted value of 1.3 and reflected the persistence of linear pharmacokinetics.This publication has 9 references indexed in Scilit:
- Pharmacokinetics and tissue penetration of Ro 23-6240, a new trifluoroquinoloneAntimicrobial Agents and Chemotherapy, 1987
- In vitro activity of Ro 23-6240, a new difluoroquinolone derivative, compared with that of other antimicrobial agentsAntimicrobial Agents and Chemotherapy, 1986
- Pharmacokinetics of a new quinolone, AM-833, in mice, rats, rabbits, dogs, and monkeysAntimicrobial Agents and Chemotherapy, 1986
- In vitro activity of Ro 23-6240, a new fluorinated 4-quinoloneAntimicrobial Agents and Chemotherapy, 1986
- Noncompartmental Determination of the Steady-State Volume of Distribution for Any Mode of AdministrationJournal of Pharmaceutical Sciences, 1982
- The interaction between indomethacin and probenecid; A clinical and pharmacokinetic studyClinical Pharmacology & Therapeutics, 1978
- Effect of Probenecid on the Blood Levels and Urinary Excretion of CefamandoleAntimicrobial Agents and Chemotherapy, 1977
- EFFECTS OF PROBENECID UPON INDIVIDUAL COMPONENTS OF INDOMETHACIN ELIMINATION1977
- EXPERIMENTAL CHANGES IN LIVER FUNCTION INDUCED BY PROBENECID1960