This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ASM journals
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stass, H.
Right arrow Articles by Schühly, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stass, H.
Right arrow Articles by Schühly, U.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 1998, p. 2060-2065, Vol. 42, No. 8
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Pharmacokinetics, Safety, and Tolerability of Ascending Single Doses of Moxifloxacin, a New 8-Methoxy Quinolone, Administered to Healthy Subjects

H. Stass,* A. Dalhoff, D. Kubitza, and U. Schühly

Pharma Research Center, Institute of Clinical Pharmacology, Bayer AG, 42096 Wuppertal, Germany

Received 3 November 1997/Returned for modification 31 March 1998/Accepted 24 May 1998

The pharmacokinetics of moxifloxacin were investigated in six studies after oral administration of 50, 100, 200, 400, 600, and 800 mg. Eight healthy male volunteers were included in each study. With doses of up to 200 mg the study was performed as a double-blind, randomized group comparison (n = 6 verum and n = 2 matched placebo); with the higher doses the study was conducted with a double-blind, randomized, crossover design. Safety and tolerability were assessed by evaluation of vital signs, electrocardiograms, electroencephalograms, clinical chemistry parameters, results of urinalysis, and adverse events. The drug was well tolerated. The concentrations of moxifloxacin in plasma, urine, and saliva were determined by a validated high-pressure liquid chromatography assay with fluorescence detection. In addition, plasma and urine samples were analyzed by a bioassay. A good correlation between both methods was seen, indicating an absence of major active metabolites. The mean maximum concentrations of moxifloxacin in plasma (Cmax) ranged from 0.29 mg/liter (50-mg dose) to 4.73 mg/liter (800-mg dose) and were reached 0.5 to 4 h following drug administration. After reaching the Cmax, plasma moxifloxacin concentrations declined in a biphasic manner. Within 4 to 5 h they fell to about 30 to 55% of the Cmax, and thereafter a terminal half-life of 11 to 14 h accounted for the major part of the area under the concentration-time curve (AUC). During the absorption phase concentrations in saliva were even higher than those in plasma, whereas in the terminal phase a constant ratio of the concentration in saliva/concentration in plasma of between 0.5 and 1 was observed, indicating a correlation between unbound concentrations in plasma and levels in saliva (protein binding level, approximately 48%). AUC and Cmax increased proportionally to the dose over the whole range of doses investigated. Urinary excretion amounted to approximately 20% of the dose. Data on renal clearance (40 to 51 ml/min/1.73 m2) indicated partial tubular reabsorption of the drug. The pharmacokinetic parameters derived from compartmental and noncompartmental analyses were in good agreement. The kinetics could be described best by fitting the data to a two-compartment body model.

* Corresponding author. Mailing address: Institute of Clinical Pharmacology, Bayer AG, Aprather Weg, Bldg. 405, D-42096 Wuppertal, Germany. Phone: 49-202-364289. Fax: 49-202-368998. E-mail: heino.stass.hs{at}bayer-ag.de.

Antimicrobial Agents and Chemotherapy, August 1998, p. 2060-2065, Vol. 42, No. 8
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Credito, K., Kosowska-Shick, K., McGhee, P., Pankuch, G. A., Appelbaum, P. C. (2010). Comparative Study of the Mutant Prevention Concentrations of Moxifloxacin, Levofloxacin, and Gemifloxacin against Pneumococci. Antimicrob. Agents Chemother. 54: 673-677 [Abstract] [Full Text]  
  • Chung, D. T., Tsai, C.-Y., Chen, S.-J., Chang, L.-W., King, C.-H. R., Hsu, C.-H., Chiu, K.-M., Tan, H.-C., Chang, Y.-T., Hsu, M.-C. (2010). Multiple-Dose Safety, Tolerability, and Pharmacokinetics of Oral Nemonoxacin (TG-873870) in Healthy Volunteers. Antimicrob. Agents Chemother. 54: 411-417 [Abstract] [Full Text]  
  • Lin, L., Chang, L.-W., Tsai, C.-Y., Hsu, C.-H., Chung, D. T., Aronstein, W. S., Ajayi, F., Kuzmak, B., Lyon, R. A. (2010). Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Nemonoxacin (TG-873870), a Novel Potent Broad-Spectrum Nonfluorinated Quinolone, in Healthy Volunteers. Antimicrob. Agents Chemother. 54: 405-410 [Abstract] [Full Text]  
  • MacGowan, A. P., Reynolds, R., Noel, A. R., Bowker, K. E. (2009). Bacterial Strain-to-Strain Variation in Pharmacodynamic Index Magnitude, a Hitherto Unconsidered Factor in Establishing Antibiotic Clinical Breakpoints. Antimicrob. Agents Chemother. 53: 5181-5184 [Abstract] [Full Text]  
  • Skalioti, C., Tsaganos, T., Stamatiadis, D., Giamarellos-Bourboulis, E. J., Boletis, J., Kanellakopoulou, K. (2009). PHARMACOKINETICS OF MOXIFLOXACIN IN PATIENTS UNDERGOING CONTINUOUS AMBULATORY PERITONEAL DIALYSIS. pdi 29: 575-579 [Abstract] [Full Text]  
  • Malhotra-Kumar, S., Van Heirstraeten, L., Lammens, C., Chapelle, S., Goossens, H. (2009). Emergence of high-level fluoroquinolone resistance in emm6 Streptococcus pyogenes and in vitro resistance selection with ciprofloxacin, levofloxacin and moxifloxacin. J Antimicrob Chemother 63: 886-894 [Abstract] [Full Text]  
  • Landersdorfer, C. B., Kinzig, M., Hennig, F. F., Bulitta, J. B., Holzgrabe, U., Drusano, G. L., Sorgel, F., Gusinde, J. (2009). Penetration of Moxifloxacin into Bone Evaluated by Monte Carlo Simulation. Antimicrob. Agents Chemother. 53: 2074-2081 [Abstract] [Full Text]  
  • van den Boogaard, J., Kibiki, G. S., Kisanga, E. R., Boeree, M. J., Aarnoutse, R. E. (2009). New Drugs against Tuberculosis: Problems, Progress, and Evaluation of Agents in Clinical Development. Antimicrob. Agents Chemother. 53: 849-862 [Full Text]  
  • Ayalasomayajula, S., Yeh, C.-M., Vaidyanathan, S., Flannery, B., Dieterich, H. A., Howard, D., Bedigian, M. P., Dole, W. P. (2008). Effects of Aliskiren, a Direct Renin Inhibitor, on Cardiac Repolarization and Conduction in Healthy Subjects. J Clin Pharmacol 48: 799-811 [Abstract] [Full Text]  
  • Almeida, D., Nuermberger, E., Tyagi, S., Bishai, W. R., Grosset, J. (2007). In Vivo Validation of the Mutant Selection Window Hypothesis with Moxifloxacin in a Murine Model of Tuberculosis. Antimicrob. Agents Chemother. 51: 4261-4266 [Abstract] [Full Text]  
  • Ross, J D C, Cronje, H S, Paszkowski, T, Rakoczi, I, Vildaite, D, Kureishi, A, Alefelder, M, Arvis, P, Reimnitz, P, on behalf of the MAIDEN Study Group, (2006). Moxifloxacin versus ofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind, randomised trial. Sex. Transm. Infect. 82: 446-451 [Abstract] [Full Text]  
  • Czock, D., Husig-Linde, C., Langhoff, A., Schopke, T., Hafer, C., de Groot, K., Swoboda, S., Kuse, E., Haller, H., Fliser, D., Keller, F., Kielstein, J. T. (2006). Pharmacokinetics of Moxifloxacin and Levofloxacin in Intensive Care Unit Patients Who Have Acute Renal Failure and Undergo Extended Daily Dialysis. CJASN 1: 1263-1268 [Abstract] [Full Text]  
  • Burman, W. J., Goldberg, S., Johnson, J. L., Muzanye, G., Engle, M., Mosher, A. W., Choudhri, S., Daley, C. L., Munsiff, S. S., Zhao, Z., Vernon, A., Chaisson, R. E., and the Tuberculosis Trials Consortium, (2006). Moxifloxacin versus Ethambutol in the First 2 Months of Treatment for Pulmonary Tuberculosis. Am. J. Respir. Crit. Care Med. 174: 331-338 [Abstract] [Full Text]  
  • Malincarne, L., Ghebregzabher, M., Moretti, M. V., Egidi, A. M., Canovari, B., Tavolieri, G., Francisci, D., Cerulli, G., Baldelli, F. (2006). Penetration of moxifloxacin into bone in patients undergoing total knee arthroplasty. J Antimicrob Chemother 57: 950-954 [Abstract] [Full Text]  
  • Esposito, S., Noviello, S., D'Errico, G., Motta, G., Passali, D., Aimoni, C., Pilucchi, S., Fallani, S., Cassetta, M. I., Mazzei, T., Novelli, A. (2006). Concentration of moxifloxacin in plasma and tonsillar tissue after multiple administration in adult patients. J Antimicrob Chemother 57: 789-792 [Abstract] [Full Text]  
  • Barcia-Macay, M., Seral, C., Mingeot-Leclercq, M.-P., Tulkens, P. M., Van Bambeke, F. (2006). Pharmacodynamic Evaluation of the Intracellular Activities of Antibiotics against Staphylococcus aureus in a Model of THP-1 Macrophages. Antimicrob. Agents Chemother. 50: 841-851 [Abstract] [Full Text]  
  • Wu, L., Shryock, J. C., Song, Y., Belardinelli, L. (2006). An Increase in Late Sodium Current Potentiates the Proarrhythmic Activities of Low-Risk QT-Prolonging Drugs in Female Rabbit Hearts. J. Pharmacol. Exp. Ther. 316: 718-726 [Abstract] [Full Text]  
  • Noreddin, A. M., Haynes, V. L., Zhanel, G. G. (2005). Pharmacokinetics and Pharmacodynamics of the New Quinolones. Journal of Pharmacy Practice 18: 432-443 [Abstract]  
  • Ginsburg, A. S., Sun, R., Calamita, H., Scott, C. P., Bishai, W. R., Grosset, J. H. (2005). Emergence of Fluoroquinolone Resistance in Mycobacterium tuberculosis during Continuously Dosed Moxifloxacin Monotherapy in a Mouse Model. Antimicrob. Agents Chemother. 49: 3977-3979 [Abstract] [Full Text]  
  • Ittner, K. P., Roth, G., Gruber, M., Pawlik, M., Taeger, K. (2005). Clearance of moxifloxacin during continuous haemofiltration (CVVHF) in vitro. J Antimicrob Chemother 56: 360-364 [Abstract] [Full Text]  
  • Firsov, A. A., Lubenko, I. Y., Vostrov, S. N., Portnoy, Y. A., Zinner, S. H. (2005). Antistaphylococcal Effect Related to the Area under the Curve/MIC Ratio in an In Vitro Dynamic Model: Predicted Breakpoints versus Clinically Achievable Values for Seven Fluoroquinolones. Antimicrob. Agents Chemother. 49: 2642-2647 [Abstract] [Full Text]  
  • Fuhrmann, V., Schenk, P., Jaeger, W., Ahmed, S., Thalhammer, F. (2004). Pharmacokinetics of moxifloxacin in patients undergoing continuous venovenous haemodiafiltration. J Antimicrob Chemother 54: 780-784 [Abstract] [Full Text]  
  • Nuermberger, E. L., Yoshimatsu, T., Tyagi, S., O'Brien, R. J., Vernon, A. N., Chaisson, R. E., Bishai, W. R., Grosset, J. H. (2004). Moxifloxacin-containing Regimen Greatly Reduces Time to Culture Conversion in Murine Tuberculosis. Am. J. Respir. Crit. Care Med. 169: 421-426 [Abstract] [Full Text]  
  • Zinner, S. H., Lubenko, I. Yu., Gilbert, D., Simmons, K., Zhao, X., Drlica, K., Firsov, A. A. (2003). Emergence of resistant Streptococcus pneumoniae in an in vitro dynamic model that simulates moxifloxacin concentrations inside and outside the mutant selection window: related changes in susceptibility, resistance frequency and bacterial killing. J Antimicrob Chemother 52: 616-622 [Abstract] [Full Text]  
  • Firsov, A. A., Vostrov, S. N., Lubenko, I. Y., Drlica, K., Portnoy, Y. A., Zinner, S. H. (2003). In Vitro Pharmacodynamic Evaluation of the Mutant Selection Window Hypothesis Using Four Fluoroquinolones against Staphylococcus aureus. Antimicrob. Agents Chemother. 47: 1604-1613 [Abstract] [Full Text]  
  • Stein, G. E., Schooley, S., Tyrrell, K. L., Citron, D. M., Goldstein, E. J. C. (2003). Bactericidal Activities of Methoxyfluoroquinolones Gatifloxacin and Moxifloxacin against Aerobic and Anaerobic Respiratory Pathogens in Serum. Antimicrob. Agents Chemother. 47: 1308-1312 [Abstract] [Full Text]  
  • Ince, D., Zhang, X., Hooper, D. C. (2003). Activity of and Resistance to Moxifloxacin in Staphylococcus aureus. Antimicrob. Agents Chemother. 47: 1410-1415 [Abstract] [Full Text]  
  • Firsov, A. A., Zinner, S. H., Vostrov, S. N., Portnoy, Y. A., Lubenko, I. Yu. (2002). AUC/MIC relationships to different endpoints of the antimicrobial effect: multiple-dose in vitro simulations with moxifloxacin and levofloxacin. J Antimicrob Chemother 50: 533-539 [Abstract] [Full Text]  
  • Madaras-Kelly, K. J., Daniels, C., Hegbloom, M., Thompson, M. (2002). Pharmacodynamic characterization of efflux and topoisomerase IV-mediated fluoroquinolone resistance in Streptococcus pneumoniae. J Antimicrob Chemother 50: 211-218 [Abstract] [Full Text]  
  • MacKenzie, F. M., Milne, K. E., Gould, I. M. (2002). Calculation of composite recovery time: a new pharmacodynamic parameter. J Antimicrob Chemother 50: 281-284 [Abstract] [Full Text]  
  • Yoshimatsu, T., Nuermberger, E., Tyagi, S., Chaisson, R., Bishai, W., Grosset, J. (2002). Bactericidal Activity of Increasing Daily and Weekly Doses of Moxifloxacin in Murine Tuberculosis. Antimicrob. Agents Chemother. 46: 1875-1879 [Abstract] [Full Text]  
  • Gehanno, P., Darantiere, S., Dubreuil, C., Chobaut, J. C., Bobin, S., Pages, J. C., Renou, G., Bobin, F., Arvis, P., Stass, H. (2002). A prospective, multicentre study of moxifloxacin concentrations in the sinus mucosa tissue of patients undergoing elective surgery of the sinus. J Antimicrob Chemother 49: 821-826 [Abstract] [Full Text]  
  • Weigel, L. M., Anderson, G. J., Facklam, R. R., Tenover, F. C. (2001). Genetic Analyses of Mutations Contributing to Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45: 3517-3523 [Abstract] [Full Text]  
  • Entenza, J. M., Que, Y. A., Vouillamoz, J., Glauser, M. P., Moreillon, P. (2001). Efficacies of Moxifloxacin, Ciprofloxacin, and Vancomycin against Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus Expressing Various Degrees of Ciprofloxacin Resistance. Antimicrob. Agents Chemother. 45: 3076-3083 [Abstract] [Full Text]  
  • GILLESPIE, S. H., MORRISSEY, I., EVERETT, D. (2001). A comparison of the bactericidal activity of quinolone antibiotics in a Mycobacterium fortuitum model. J Med Microbiol 50: 565-570 [Abstract] [Full Text]  
  • Bermudez, L. E., Inderlied, C. B., Kolonoski, P., Petrofsky, M., Aralar, P., Wu, M., Young, L. S. (2001). Activity of Moxifloxacin by Itself and in Combination with Ethambutol, Rifabutin, and Azithromycin In Vitro and In Vivo against Mycobacterium avium. Antimicrob. Agents Chemother. 45: 217-222 [Abstract] [Full Text]  
  • Firsov, A. A., Lubenko, I. Yu., Vostrov, S. N., Kononenko, O. V., Zinner, S. H., Portnoy, Y. A. (2000). Comparative pharmacodynamics of moxifloxacin and levofloxacin in an in vitro dynamic model: prediction of the equivalent AUC/MIC breakpoints and equiefficient doses. J Antimicrob Chemother 46: 725-732 [Abstract] [Full Text]  
  • Lubasch, A., Keller, I., Borner, K., Koeppe, P., Lode, H. (2000). Comparative Pharmacokinetics of Ciprofloxacin, Gatifloxacin, Grepafloxacin, Levofloxacin, Trovafloxacin, and Moxifloxacin after Single Oral Administration in Healthy Volunteers. Antimicrob. Agents Chemother. 44: 2600-2603 [Abstract] [Full Text]  
  • Pestova, E., Millichap, J. J., Noskin, G. A., Peterson, L. R. (2000). Intracellular targets of moxifloxacin: a comparison with other fluoroquinolones. J Antimicrob Chemother 45: 583-590 [Abstract] [Full Text]  
  • MacGowan, A. P., Bowker, K. E., Wootton, M., Holt, H. A. (1999). Exploration of the in-vitro pharmacodynamic activity of moxifloxacin for Staphylococcus aureus and streptococci of Lancefield Groups A and G. J Antimicrob Chemother 44: 761-766 [Abstract] [Full Text]  
  • Sullivan, J. T., Woodruff, M., Lettieri, J., Agarwal, V., Krol, G. J., Leese, P. T., Watson, S., Heller, A. H. (1999). Pharmacokinetics of a Once-Daily Oral Dose of Moxifloxacin (Bay 12-8039), a New Enantiomerically Pure 8-Methoxy Quinolone. Antimicrob. Agents Chemother. 43: 2793-2797 [Abstract] [Full Text]  
  • Wilson, R., Kubin, R., Ballin, I., Deppermann, K.-M., Bassaris, H. P., Leophonte, P., Schreurs, A. J. M., Torres, A., Sommerauer, B. (1999). Five day moxifloxacin therapy compared with 7 day clarithromycin therapy for the treatment of acute exacerbations of chronic bronchitis. J Antimicrob Chemother 44: 501-513 [Abstract] [Full Text]  
  • Muller, M., Sta{beta}, H., Brunner, M., Moller, J. G., Lackner, E., Eichler, H. G. (1999). Penetration of Moxifloxacin into Peripheral Compartments in Humans. Antimicrob. Agents Chemother. 43: 2345-2349 [Abstract] [Full Text]  
  • Wise, R., Andrews, J. M., Marshall, G., Hartman, G. (1999). Pharmacokinetics and Inflammatory-Fluid Penetration of Moxifloxacin following Oral or Intravenous Administration. Antimicrob. Agents Chemother. 43: 1508-1510 [Abstract] [Full Text]  
  • Miyazaki, E., Miyazaki, M., Chen, J. M., Chaisson, R. E., Bishai, W. R. (1999). Moxifloxacin (BAY12-8039), a New 8-Methoxyquinolone, Is Active in a Mouse Model of Tuberculosis. Antimicrob. Agents Chemother. 43: 85-89 [Abstract] [Full Text]  
  • Ji, B., Lounis, N., Maslo, C., Truffot-Pernot, C., Bonnafous, P., Grosset, J. (1998). In Vitro and In Vivo Activities of Moxifloxacin and Clinafloxacin against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 42: 2066-2069 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»