Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1992 Jun;36(6):1296–1301. doi: 10.1128/aac.36.6.1296

Multiple-dose pharmacokinetics and safety of rufloxacin in normal volunteers.

J C Kisicki 1, R S Griess 1, C L Ott 1, G M Cohen 1, R J McCormack 1, W M Troetel 1, B P Imbimbo 1
PMCID: PMC190335  PMID: 1329618

Abstract

The pharmacokinetics and safety of rufloxacin were evaluated in a double-blind, placebo-controlled study. Two groups of 16 healthy volunteers were given a single oral loading dose of 400 or 600 mg of rufloxacin on day 1 of the study. A single daily maintenance dose of 200 or 300 mg was then administered for a further 9 days; in addition, four subjects in each group received placebos. Rufloxacin levels in plasma and urine were determined by high-performance liquid chromatography. Following the initial dose, the mean (+/- standard error of the mean) peak concentrations of rufloxacin in plasma were 3.35 +/- 0.12 micrograms/ml in the 400-mg group and 4.54 +/- 0.19 micrograms/ml in the 600-mg group. They were generally reached 2 to 3 h after dosing. At the end of treatment, maximum levels in plasma rose to 4.51 +/- 0.15 and 7.20 +/- 0.25 micrograms/ml in the 400-mg and 600-mg groups, with a mean extent of accumulation (fold) of 3.1 +/- 0.1 and 3.3 +/- 0.1. For the 400-mg and 600-mg groups, the elimination half-lives were 40.0 +/- 1.5 and 44.0 +/- 1.3 h, mean residence times were 57.8 +/- 2.2 and 63.7 +/- 1.8 h, apparent volumes of distribution were 132 +/- 4 and 139 +/- 5 liters, and apparent total body clearance were 39 +/- 1 and 44 +/- 4 ml/min, assuming complete bioavailability. Of the total dose administered, the percentages excreted in urine were 49.6 +/- 1.3 and 51.1 +/-2.1%, with renal clearances of 21 +/- 1 and 22 +/- 2 ml/min, for the 400-mg and 600-mg groups. On the whole, the treatments were well tolerated, but some minor adverse events (mainly headache, insomnia, or abdominal discomfort) were reported for 7 subjects on abnormalities were detected in the laboratory examinations or in ocular function tests. This study shows that a 200-mg daily oral dose of rufloxacin preceded by a loading dose of 400 mg are well tolerated and produce steady-state concentrations in plasma above the MIC for most susceptible pathogens.

Full text

PDF
1296

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cecchetti V., Fravolini A., Fringuelli R., Mascellani G., Pagella P., Palmioli M., Segre G., Terni P. Quinolonecarboxylic acids. 2. Synthesis and antibacterial evaluation of 7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzothiazine-6-carboxylic acids. J Med Chem. 1987 Mar;30(3):465–473. doi: 10.1021/jm00386a005. [DOI] [PubMed] [Google Scholar]
  2. Colburn W. A. Estimating the accumulation of drugs. J Pharm Sci. 1983 Jul;72(7):833–834. doi: 10.1002/jps.2600720734. [DOI] [PubMed] [Google Scholar]
  3. Gibaldi M., Levy G., McNamara P. J. Effect of plasma protein and tissue binding on the biologic half-life of drugs. Clin Pharmacol Ther. 1978 Jul;24(1):1–4. doi: 10.1002/cpt19782411. [DOI] [PubMed] [Google Scholar]
  4. Imbimbo B. P., Broccali G., Cesana M., Crema F., Attardo-Parrinello G. Inter- and intrasubject variabilities in the pharmacokinetics of rufloxacin after single oral administration to healthy volunteers. Antimicrob Agents Chemother. 1991 Feb;35(2):390–393. doi: 10.1128/aac.35.2.390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Imbimbo B. P., Imbimbo E., Daniotti S., Verotta D., Bassotti G. A new criterion for selection of pharmacokinetic multiexponential equations. J Pharm Sci. 1988 Sep;77(9):784–789. doi: 10.1002/jps.2600770914. [DOI] [PubMed] [Google Scholar]
  6. Mattina R., Cocuzza C. E., Cesana M., Bonfiglio G. In vitro activity of a new quinolone, rufloxacin, against nosocomial isolates. Chemotherapy. 1991;37(4):260–269. doi: 10.1159/000238865. [DOI] [PubMed] [Google Scholar]
  7. Ravizzola G., Pinsi G., Pirali F., Colombrita D., Foresti I., Peroni L., Turano A. Rufloxacin (MF-934): in vitro and in vivo antibacterial activity. Drugs Exp Clin Res. 1989;15(1):11–15. [PubMed] [Google Scholar]
  8. Segre G., Cerretani D., Cerri D., Moltoni L. A new tricyclic fluoroquinolone, rufloxacin (MF-934), with interesting antibacterial and pharmacokinetic characteristics. Drugs Exp Clin Res. 1988;14(12):747–754. [PubMed] [Google Scholar]
  9. Wise R., Johnson J., O'Sullivan N., Andrews J. M., Imbimbo B. P. Pharmacokinetics and tissue penetration of rufloxacin, a long acting quinolone antimicrobial agent. J Antimicrob Chemother. 1991 Dec;28(6):905–909. doi: 10.1093/jac/28.6.905. [DOI] [PubMed] [Google Scholar]
  10. Wolfson J. S., Hooper D. C. Pharmacokinetics of quinolones: newer aspects. Eur J Clin Microbiol Infect Dis. 1991 Apr;10(4):267–274. doi: 10.1007/BF01967000. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES