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.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baber N., Halliday L., Sibeon R., Littler T., Orme M. L. The interaction between indomethacin and probenecid. A clinical and pharmacokinetic study. Clin Pharmacol Ther. 1978 Sep;24(3):298–307. doi: 10.1002/cpt1978243298. [DOI] [PubMed] [Google Scholar]
- Chin N. X., Brittain D. C., Neu H. C. In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone. Antimicrob Agents Chemother. 1986 Apr;29(4):675–680. doi: 10.1128/aac.29.4.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duggan D. E., Hooke K. F., White S. D., Noll R. M., Stevenson C. R. The effects of probenecid upon the individual components of indomethacin elimination. J Pharmacol Exp Ther. 1977 May;201(2):463–470. [PubMed] [Google Scholar]
- GOETZEE A. E., RICHARDS T. G., TINDALL V. R. Experimental changes in liver function induced by probenecid. Clin Sci. 1960 Feb;19:63–78. [PubMed] [Google Scholar]
- Griffith R. S., Black H. R., Brier G. L., Wolny J. D. Effect of probenecid on the blood levels and urinary excretion of cefamandole. Antimicrob Agents Chemother. 1977 May;11(5):809–812. doi: 10.1128/aac.11.5.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kusajima H., Ishikawa N., Machida M., Uchida H., Irikura T. Pharmacokinetics of a new quinolone, AM-833, in mice, rats, rabbits, dogs, and monkeys. Antimicrob Agents Chemother. 1986 Aug;30(2):304–309. doi: 10.1128/aac.30.2.304. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Manek N., Andrews J. M., Wise R. In vitro activity of Ro 23-6240, a new difluoroquinolone derivative, compared with that of other antimicrobial agents. Antimicrob Agents Chemother. 1986 Aug;30(2):330–332. doi: 10.1128/aac.30.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perrier D., Mayersohn M. Noncompartmental determination of the steady-state volume of distribution for any mode of administration. J Pharm Sci. 1982 Mar;71(3):372–373. doi: 10.1002/jps.2600710332. [DOI] [PubMed] [Google Scholar]
- Wise R., Kirkpatrick B., Ashby J., Griggs D. J. Pharmacokinetics and tissue penetration of Ro 23-6240, a new trifluoroquinolone. Antimicrob Agents Chemother. 1987 Feb;31(2):161–163. doi: 10.1128/aac.31.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]