Fleroxacin Clinical Pharmacokinetics
Tóm tắt
Fleroxacin is a new member of the class of fluoroquinolones. The drug has good activity (i.e. minimum inhibitory concentrations at less than 2 mg/L against 90% of strains) against a wide range of Gram-positive and Gram-negative bacteria. High performance liquid chromatography is used to determine concentrations of fleroxacin and its metabolites in biological fluids. Absorption of orally ingested drug is rapid as the peak plasma concentration of approximately 5 mg/L is reached in 1 to 2h after a single dose of 400mg. The systemic availability is close to 100%. Fleroxacin is poorly bound to plasma proteins (23%) and exhibits excellent tissue distribution. Renal clearance accounts for 60 to 70% of elimination. The drug is metabolised to form antimicrobially active N-demethyl-fleroxacin and inactive N-oxide-fleroxacin. In multiple dose studies the accumulation ratio of a once-daily dosage regimen is about 1.3, as predicted from the elimination half-life of 10 to 12h. Compared with ciprofloxacin, fleroxacin has a greater systemic availability and a longer half-life. Fleroxacin concentrations are higher in elderly patients, but further studies are needed to establish whether a dosage reduction should be recommended for this age group. In patients with renal disease dosage adjustment is recommended since a decreased renal clearance of fleroxacin leads to a significant prolongation of the elimination half-life. Fleroxacin is only poorly eliminated by peritoneal dialysis or haemodialysis. The most important drug-drug interaction is a decrease in systemic availability of fleroxacin after ingestion of aluminium- or magnesium-containing antacids. There is no evidence of a significant interaction between fleroxacin and theophylline. Only limited data are available on adverse reactions of fleroxacin. The most important adverse effects appear to be photosensitivity and a dose-dependent incidence of central nervous system reactions including sleep disorders.
Tài liệu tham khảo
Abeck D, Johnson AP, Alexander F, Korting HC, Ballard RC. In vitro activity of eight antimicrobial agents against non-penicillinase-producing gonococci isolated in Munich. Genitourinary Medicine 64: 233–234, 1988
Aldridge KE, Schiro DD, Sanders CV. RO23-6240. a new orally absorbed quinolone: in vitro comparison with other broad spectrum oral antimicrobial agents and imipemen. Diagnostic Microbiology and Infectious Disease 7: 9–19, 1987
Aoyama H, Inoue M, Mitsuhashi S. In-vitro and in-vivo antibacterial activity of fleroxacin, a new fluorinated quinolone. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 99–114 1988
Appelbaum PC, Spangler SK, Tamarree T. Susceptibility of 310 nonfermentative gram-negative bacteria to azteonam, carumonam, ciprofloxacin, ofloxacin, and fleroxacin. Chemotherapy 34: 40–45, 1988
Awni WM, Maloney JA, Heim-Duthoy KL. Liquid-chromatographic determination of fleroxacin in serum and urine. Clinical Chemistry 34: 2330–2332, 1988
Baba S, Mori Y, Maruo T. Penetration of fleroxacin into maxillary sinus mucosa and palatine tonsil. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 195–197, 1988
Bergeron MG. The pharmacokinetics and tissue penetration of the fluoroquinolones. Clinical and Investigative Medicine 12: 20–27, 1989
Bowie WR, Willetts V, Jewesson PJ. Adverse reactions in a dose-ranging study with a new long-acting fluoroquinolone, fleroxacin. Antimicrobial Agents and Chemotherapy 33: 1778–1782, 1989
Bowie WR, Willetts V, Megran DW. Dose-ranging study of fleroxacin for treatment of uncomplicated chlamydia trachomatis genital infections. Antimicrobial Agents and Chemotherapy 33: 1774–1777, 1989
Bremner DA, Dickie AS, Singh KP. In-vitro activity of fleroxacin compared with three other quinolones. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 19–23, 1988
Chin NX, Brittain DC, Neu HC. In-vitro activity of Ro 23-6240, a new fluorinated 4-quinolone. Antimicrobial Agents and Chemotherapy 29: 675–680, 1986
Clarke AM, Zemcov SJV. In vitro activity of the new 4-quinolone compound Ro 23-6240. European Journal of Clinical Microbiology 6: 161–164, 1987
De Lepeleire I, Van Hecken A, Verbesselt R, Tjandra-Maga TB, Schepper PJ. Comparative oral pharmacokinetics of fleroxacin and pefloxacin. Journal of Antimicrobial Chemotherapy 22: 197–202, 1988
Decazes JM, Mohler J, Bure A, Vallois JM, Meulemans A, et al. Pharmacokinetics of fleroxacin and its metabolites in serum, cerebrospinal fluid, and brain of rabbits with and without experimental Escherichia coli meningitis. Reviews of Infectious Diseases 11 (Suppl. 5): S1208–S1209, 1989
Dell D, Partos C, Portmann R. The determination of a new trifluorinated quinolone, fleroxacin, its N-demethyl, and N-oxide metabolites in plasma and urine by high performance liquid chromatography with fluorescence detection. Journal of Liquid Chromatography 11: 1299–1312, 1988
Digranes A, Benonisen E, Salveson A, Zahm F. In vitro studies of fleroxacin (Ro 23-6240), a new trifluorinated quinolone derivative. Chemotherapy 34: 401–410, 1988
Dubois J, Fontaine V. In-vitro activity of fleroxacin against urinary tract and genital tract pathogens. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 31–34, 1988
Easmon CSF, Woodford N, Ison CA. The activity of the 4 quinolone Ro 23 6240 and the cephalosporins Ro 15 8074 and Ro 19 5247 against penicillin sensitive and resistant gonococci. Journal of Antimicrobial Chemotherapy 19: 761–765, 1987
Edwards DJ, Bowles SK, Svensson CK, Rybak MJ. Inhibition of drug metabolism by quinolone antibiotics. Clinical Pharmacokinetics 15: 194–204, 1988
Ernst F, van der Auwera P. In-vitro activity of fleroxacin (Ro 23-6240), a new fluoro-quinolone, and other agents, against Mycobacterium spp. Journal of Antimicrobial Chemotherapy 21: 501–504, 1988
Fass RJ, Helsel VL. In vitro activity of RO 23-6240 (AM-833): a new fluoroquinolone. Diagnostic Microbiology and Infectious Disease 6: 293–299, 1987
Fuchs PC, Jones RN, Barry AL, Ayers LW, Gavan TL, et al. RO 23-6240 (AM-833), a new fluoroquinolone: in vitro antimicrobial activity and tentative disk diffusion interpretive criteria. Diagnostic Microbiology and Infectious Disease 7: 29–35, 1987
Georgopoulos A, Breyer S, Georgopoulos M, Mailer H, Graninger W. In-vitro activity of fleroxacin. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 25–29, 1988
Griggs DJ, Wise R. A simple isocratic high-pressure liquid Chromatographic assay of quinolones in serum. Journal of Antimicrobial Chemotherapy 24: 437–445, 1989
Griggs DJ, Wise R, Kirkpatrick B, Ashby JP. The metabolism and pharmacokinetics of fleroxacin in healthy subjects. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 191–194, 1988
Heim-Duthoy K, Peltier G, Awni W. Steady-state pharmacokinetics of fleroxacin in patients with skin and skin structure infections. Antimicrobial Agents and Chemotherapy 34: 922–923, 1990
Heizmann P, Dell D, Eggers H, Gora R. Determination of the new fluoroquinolone fleroxacin and its N-demethyl and N-oxide metabolites in plasma and urine by high-performance liquid chromatography with fluorescence detection. Journal of Chromatography 527: 91–101, 1990
Hellum KB, Walstad RA, Thurmann-Nielsen E, Dale LG. Fleroxacin: pharmacokinetics and penetration into interstitial fluid. Reviews of Infectious Diseases 11 (Suppl. 5): S1081–S1082, 1989
Hirai K, Aoyama H, Hosaka M, et al. In vitro and in vivo antibacterial activity of AM-833, a new quinolone derivative. Antimicrobial Agents and Chemotherapy 29: 1059–1066, 1986
Hohl P, Luthy-Hottenstein J, Zollinger-Iten J, Altwegg M. In vitro activities of fleroxacin, cefetamet, ciprofloxacin, ceftriaxone, trimethoprim-sulfamethoxazole, and amoxicillin-clavulanic acid against rare members of the family Enterobacteriaceae primarily of human (clinical) origin. Antimicrobial Agents and Chemotherapy 34: 1605–1608, 1990
Hohl P, Salfinger M, Kafader FM. In vitro activity of the new quinolone RO 23-6240 (AM-833) and the new cephalosporins RO 15-8074 and RO 19-5247 (T-2525) against Mycobacterium fortuitum and Mycobacterium chelonae. European Journal of Clinical Microbiology 6: 487–488, 1987a
Hohl P, von Graevenitz A, Zollinger-Iten J. Fleroxacin (Ro 23-6240): activity in vitro against 355 enteropathogenic and non-fermentative Gram-negative bacilli and Legionella pneumophila. Journal of Antimicrobial Chemotherapy 20: 373–378, 1987b
Hosaka M, Gotoh N, Nishino T. In vitro and in vivo antibacterial activities of fleroxacin. Reviews of Infectious Diseases 11 (Suppl. 5): S954–S955, 1989
Jedlickova Z, Kubin M, Lonska V, Laznickova T. Activity of fleroxacin in vitro. Reviews of Infectious Diseases 11 (Suppl. 5): S987, 1989
Jynge P, Skjetne T, Gribbestad I, Kleinbloesem CH, Hoogkamer HFW, et al. In vivo tissue pharmacokinetics by fluorine magnetic resonance spectroscopy: a study of liver and muscle disposition of fleroxacin in humans. Clinical Pharmacology and Therapeutics 48: 481–489, 1990
Kaukoranta-Tolvanen SSE, Renkonen OVJ. In vitro susceptibility of Neisseria gonorrhoeae to RO 23-6240 and ciprofloxacin. European Journal of Clinical Microbiology 6: 315–317, 1987
Kees F, Naber KG, Schumacher H, Grobecker H. Penetration of fleroxacin into prostatic secretion and prostatic adenoma tissue. Chemotherapy 34: 437–443, 1988
Kenny GE, Hooton TM, Roberts MC, Cartwright FD, Hoyt J. Susceptibilities of genital mycoplasmas to the newer quinolones as determined by the agar dilution method. Antimicrobial Agents and Chemotherapy 33: 103–107, 1989
Khardori N, Reuben A, Rosenbaum B, Rolston K, Bodey GP. In vitro susceptibility of Xanthomonas (Pseudomonas) maltophilia to newer antimicrobial agents. Antimicrobial Agents and Chemotherapy 34: 1609–1610, 1990
Koechlin C, Jehl F, Linger L, Monteil H. High-performance liquid chromatography for the determination of three new fluoroquinolones, fleroxacin, temafloxacin and A-64730, in biological fluids. Journal of Chromatography 491: 379–387, 1989
Krausse R, Ullmann U. Comparative in vitro activity of fleroxacin (RO 23-6240) against Ureaplasma urealyticum and Mycoplasma hominis. European Journal of Clinical Microbiology and Infectious Diseases 7: 67–69, 1988
Kropec A, Daschner F. In vitro activity of fleroxacin and 6 other antimicrobials against Acinetobacter anitratus. Chemotherapy 35: 360–362, 1989a
Kropec A, Daschner F. In vitro activity of fleroxacin and 14 other antimicrobials against slime- and non-slime-producing Staphylococcus epidermidis. Chemotherapy 35: 351–354, 1989b
Laznickova T, Jedlickova Z, Kubin M, Seremek O. The antimicrobial activity of fleroxacin Ro 23-6240, a third generation fluoroquinolone derivative, tested in vitro. Journal of Hygiene, Epidemiology, Microbiology and Immunology 34: 77–80, 1990
Le Saux NM, Slaney LA, Plummer FA, Ronald AR, Brunham RC. In vitro activity of ceftriaxone, cefetamet (Ro 15-8074), ceftetrame (Ro 19-5247; T-2588), and fleroxacin (Ro 23-6240; AM-833) versus Neisseria gonorrhoeae and Haemophilus ducreyi. Antimicrobial Agents and Chemotherapy 31: 1153–1154, 1987
Lefevre JC, Gaubert E, Lareng MB. Activité in vitro de cinq nouvelles quinolones sur Gardnerella vaginalis. Pathologie Biologie 37: 394–396, 1989
Leibovitz E, Keren G, Shabtai M, Barzilai A, Rubinstein E. The pharmacokinetics and therapeutic efficacy of fleroxacin and pefloxacin in a rat abscess model. Journal of Antimicrobial Chemotherapy 24: 375–385, 1989
Lode H, Hoffken G, Borner K, Koeppe P. Unique aspects of quinolone pharmacokinetics. Clinical Pharmacokinetics 16 (Suppl. 1): 1–4, 1989
Machka K, Balg H, Braveny I. In vitro activity of new antibiotics against Haemophilus influenzae. European Journal of Clinical Microbiology and Infectious Diseases 7: 812–814, 1988
Machka K, Braveny I. Comparative in vitro activity of Ro 23-6240 (Fleroxacin), a new 4-quinolone derivative. European Journal of Clinical Microbiology 6: 482–485, 1987
Maeda H, Fujii A, Nakata K, Arakawa S, Kamidono S. In vitro activities of T-3262, NY-198, fleroxacin (AM-833; RO 23-6240) and other new quinolone agents against clinically isolated Chlamydia trachomatis strains. Antimicrobial Agents and Chemotherapy 32: 1080–1081, 1988
Metz R, Hoffler D, Sörgel F, Seelmann R, Koeppe P, et al. Pharmacokinetics and metabolism of fleroxacin in patients with renal impairment. Reviews of Infectious Diseases 11 (Suppl. 5): S1011–S1012, 1989
Mimeault J, Ruel M, Bergeron MG, Vallee F, LeBel M. Pharmacokinetics of fleroxacin in patients with cystic fibrosis. Reviews of Infectious Diseases 11 (Suppl. 5): S1253–S1254, 1989
Mimeault J, Vallee F, Seelmann R, Sörgel F, Ruel M, et al. Altered disposition of fleroxacin in patients with cystic fibrosis. Clinical Pharmacology and Therapeutics 47: 618–628, 1990
Mondorf AW, Buch A, Steinbacher G, Rudel C, Falkenberg FW. Renal tolerance of fleroxacin in healthy volunteers. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 179–189, 1988
Naber KG, Sörgel F, Kees F, Schumacher H, Metz R, et al. In-vitro activity of fleroxacin against isolates causing complicated urinary tract infections and concentrations in seminal and prostatic fluid and in prostatic adenoma tissue. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 199–207, 1988
Nakashima M, Kanamaru M, Uematsu T, Takiguchi A, Mizuno A, et al. Clinical pharmacokinetics and tolerance of fleroxacin in healthy male volunteers. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 133–144, 1988
Neuman M. Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clinical Pharmacokinetics 14: 96–121, 1988
Paganoni R, Herzog C, Braunsteiner A, Hohl P. Fleroxacin: in-vitro activity worldwide against 20,807 clinical isolates and comparison to ciprofloxacin and norfloxacin. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 3–17, 1988
Panneton AC, Bergeron MG, LeBel M. Pharmacokinetics and tissue penetration of fleroxacin after single and multiple 400- and 800-mg-dosage regimens. Antimicrobial Agents and Chemotherapy 32: 1515–1520, 1988
Parent M, St-Laurent M, LeBel M. Safety of fleroxacin coadministered with theophylline to young and elderly volunteers. Antimicrobial Agents and Chemotherapy 34: 1249–1253, 1990
Paton JH, Reeves DS. Fluoroquinolone antibiotics: microbiology, pharmacokinetics and clinical use. Drugs 36: 193–228, 1988
Pohlod DJ, Saravolatz LD, Somerville MM. In-vitro susceptibility of staphylococci to fleroxacin in comparison with six other quinolones. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 35–41, 1988a
Pohlod DJ, Saravolatz LD, Somerville MM. Inhibition of Legionella pneumophila multiplication within human macrophages by fleroxacin. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 49–54, 1988b
Portmann R, Hansz C, Stiglmayer R, Weidekamm E. Fleroxacin concentrations in myometrium, ovary, and fallopian tube. Journal of Antimicrobial Chemotherapy 24: 662–664, 1989
Qadri SMH, Akhtar M, Ueno Y, al-Sibai MB. Susceptibility of Bruceila melitensis to fluoroquinolones. Drugs Under Experimental and Clinical Research 15: 483–485, 1989
Salfinger M, Hohl P, Kafader FM. Comparative in-vitro activity of fleroxacin and other 6-fluoroquinolones against mycobacteria. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 55–63, 1988
Seelmann R, Mahr G, Gottschalk B, Stephan U, Sörgel F. Influence of fleroxacin on the pharmacokinetics of theophylline. Reviews of Infectious Diseases 11 (Suppl. 5): S1100, 1989
Shah PM, Sammann A, Schafer V, Seczendi M, Knothe H. Fleroxacin: safety, tolerance and effect on the faecal flora of healthy volunteers. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 209–213, 1988
Shiba K, Saito A, Shimada J, Hori S, Kaji M, et al. Renal handling of fleroxacin in rabbits, dogs, and humans. Antimicrobial Agents and Chemotherapy 34: 58–64, 1990
Simor AE, Ferro S, Low DE. Comparative in vitro activities of six new fluoroquinolones and other oral antimicrobial agents against Campylobacter pylori. Antimicrobial Agents and Chemotherapy 33: 108–109, 1989
Singlas E, Leroy A, Sultan E, Fillastre JP, Godin M, et al. Pharmacokinetics of fleroxacin in healthy volunteers and in uremic patients: evaluation of two assay methods. Reviews of Infectious Diseases 11 (Suppl. 5): S1017, 1989
Singlas E, Leroy A, Sultan E, Godin M, Moulin B, et al. Disposition of fleroxacin, a new trifluoroquinolone, and its metabolites. Clinical Pharmacokinetics 19: 67–79, 1990
Sörgel F, Jaehde U, Naber K, Stephan U. Pharmacokinetic disposition of quinolones in human body fluids and tissues. Clinical Pharmacokinetics 16 (Suppl. 1): 5–24, 1989
Sörgel F, Metz R, Naber K, Seelmann R, Muth P. Pharmacokinetics and body fluid penetration of fleroxacin in healthy volunteers. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 155–167, 1988
Sörgel F, Seelmann R, Naber K, Metz R, Muth P. Metabolism of fleroxacin in man. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 169–178, 1988
Steele-Mortimer O, Meier-Ewert H. In-vitro activity of fleroxacin against Chlamydia trachomatis. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 65–70, 1988
Stein GE. The 4-quinolone antibiotics: past, present, and future. Pharmacotherapy 8: 301–314, 1988
Stobberingh E, Houben A, Van Boven C. In vitro characterization of Ro 23-6240. Chemioterapia 6 (Suppl. 2): 154–155. 1987a
Stobberingh EE, Houben AW, Van Boven CPA. In vitro evaluation of Ro 23-6240, a new fluorinated 4-quinolone. Chemotherapy 33: 197–203, 1987b
Stuck AE, Frey FJ, Heizmann P, Brandt R, Weidekamm E. Pharmacokinetics and metabolism of intravenous and oral fleroxacin in subjects with normal and impaired renal function and in patients on continuous ambulatory peritoneal dialysis. Antimicrobial Agents and Chemotherapy 33: 373–381, 1989
Taburet AM, Devillers A, Thomare P, Fillastre JP, Veyssier P, et al. Disposition of fleroxacin, a new trifluoroquinolone, and its metabolites: pharmacokinetics in elderly patients. Clinical Pharmacokinetics 19: 80–88, 1990
Traub WH, Spohr M, Bauer D. Pseudomonas aeruginosa: in vitro susceptibility to antimicrobial drugs, single and combined, with and without defibrinated blood. Chemotherapy 34: 284–297, 1988
Tudor RG, Youngs DJ, Yoshioka K, Burdon DW, Keighley MRB. A comparison of the penetration of two quinolones into intra-abdominal abscess. Archives of Surgery 123: 1487–1490. 1988
Upton RA. Pharmacokinetic interactions between theophylline and other medications. Clinical Pharmacokinetics 20: 66–80, 1991
van der Auwera P, Matsumoto T, Husson M. Intraphagocytic penetration of antibiotics. Journal of Antimicrobial Chemotherapy 225: 185–192, 1988
van der Willigen AH, Degener JE, Vogel M, Stolz E, Wagenvoort JHT. In vitro activities of seven quinolone derivatives against Neisseria gonorrhoeae. Arzneimittel-Forschung 40: 684–685, 1990
Vance-Bryan K, Guay DRP, Rotschafer JC. Clinical pharmacokinetics of ciprofloxacin. Clinical Pharmacokinetics 19: 434–461, 1990
Verbist L. Comparative in-vitro activity of Ro 23-6240. a new trifluorinated quinolone. Journal of Antimicrobial Chemotherapy 20: 363–372, 1987
Verschraegen G, Claeys G, Van den Abeele AM. Comparative in vitro activity of the new quinolone fleroxacin (RO 23-6240). European Journal of Clinical Microbiology and Infectious Diseases 7: 63–66, 1988
Verschraegen G, Claeys G, Van den Abeele AM. In vitro comparison of fleroxacin with other antimicrobial agents. Reviews of Infectious Diseases 11 (Suppl. 5): S937–S938, 1989
Weidekamm E, Portmann R. Variation of pharmacokinetic parameters after intravenous and oral administration of fleroxacin. Reviews of Infectious Diseases 11 (Suppl. 5): S1023, 1989
Weidekamm E, Portmann R, Partos C, Dell D. Single and multiple dose pharmacokinetics of fleroxacin. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 145–154. 1988a
Weidekamm E, Portmann R, Partos C, Dell D, Lucker PW. Single and multiple-dose pharmacokinetics of fleroxacin. a trifluorinated quinolone, in humans. Antimicrobial Agents and Chemotherapy 31: 1909–1914, 1987a
Weidekamm E, Stockel K, Dell D. A new trifluorinated quinolone: Ro 23-6240 (AM-833). Drugs Under Experimental and Clinical Research 13: 85–90, 1987b
Weidekamm E, Stockel K, Dell D. Single-dose pharmacokinetics of the new fluoroquinolone Ro 23-6240 (AM 833) in humans. Reviews of Infectious Diseases 10 (Suppl. 1): S94–S95, 1988b
Wise R, Kirkpatrick B, Ashby J, Griggs DJ. Pharmacokinetics and tissue penetration of Ro 23-6240, a new trifluoroquinolone. Antimicrobial Agents and Chemotherapy 31: 161–163, 1987
Wolfhagen MJHM, Hoepelman AIM, Verhoef J. Double-blind, dose-range-finding study of fleroxacin (Ro 23-6240; AM-833) for treatment of complicated urinary tract infections. Antimicrobial Agents and Chemotherapy 34: 409–412, 1990
Wolfson JS, Hooper DC. Fluoroquinolone antimicrobial agents. Clinical Microbiology Reviews 2: 378–424, 1989
Wüst J, Hardegger U. Comparative in vitro activity of cefetamet and fleroxacin against anaerobic bacteria. European Journal of Clinical Microbiology 6: 688–690, 1987
Youngs DJ, Tudor RG, Burdon DW, Keighley MRB. Penetration of fleroxacin into intraabdominal abscesses. Reviews of Infectious Diseases 11 (Suppl. 5): S1062, 1989
Youngs DJ, Tudor RG, Yoshioka K, Keighley MRB. The penetration of fleroxacin into intra-abdominal abscesses. Journal of Antimicrobial Chemotherapy 22 (Suppl. D): 115–118, 1988