Journal of Antimicrobial Chemotherapy (1999) 43, Suppl. B, 69-76
© 1999 The British Society for Antimicrobial Chemotherapy
Pharmacokinetics of the 8-methoxyquinolone, moxifloxacin: a comparison in humans and other mammalian species
Bayer AG, Pharma Research Center, Wuppertal, Germany
The pharmacokinetics of moxifloxacin was investigated in NMRI mice, Wistar rats, rhesus monkeys, beagle dogs, Göttingen minipigs and healthy human volunteers after iv and oral administration of moxifloxacin-HCl (single doses of moxifloxacin 9.2 mg/kg bodyweight) in animals and 100 mg moxifloxacin (1.4 mg/kg bodyweight po and 1.2 mg/kg bodyweight iv) in humans. The plasma concentration vs time courses of the unchanged compound (determined by HPLC) and the derived pharmacokinetic parameters were used to evaluate the absorption process, to compare the pharmacokinetics in these species and to perform an interspecies scaling. The results of the pharmacokinetic investigations indicate a clear dependence on the species. Moxifloxacin is absorbed quickly (rats, dogs, humans > monkeys): the major portion of the dose reached the systemic circulation within the first 2 h. In the minipig absorption was slower. Bioavailability was high to moderate (91–52%) in all species. Protein binding (f u) was low (55–71%) in all species. The volume of distribution at steady state (V ss) was medium to large (2.0–4.9 L/kg) in all species. There were considerable differences in maximum concentrations (C max,norm, 0.430–0.070 kg/L) and in AUC norm values (oral, 6.18–0.184 kg·h/L; iv, 7.51–0.237 kg·h/L). Total body clearance (CL) decreased with increasing bodyweight (4.21–0.132 L/(h·kg)). The mean residence time (MRT) decreased with decreasing bodyweight (15–0.88 h). The half-life (t ½) decreased with decreasing bodyweight (oral, 12–1.3 h, iv, 13–0.93 h). There was moderate to low renal excretion (iv, 20–6.2%), the renal clearance, (CL R) was in the range 0.615–0.0222 L/(h·kg). Regarding the pharmacokinetic parameters determined after oral administration, the dog was most similar to the human in terms of C max, AUC and t ½. There was good correlation between bodyweight and CL (coefficient of correlation (r) = 0.959), V ss (r = 0.990) and MRT (r = 0.943). On the basis of preclinical studies a terminal half-life appropriate for once-daily dosing in humans was predicted and confirmed by Phase I data.
* Correspondence address. Preclinical Pharmacokinetics, Pharma Research Center, Bldg 468, D-42096 Wuppertal, Germany. Tel: +49-202-36-4245; Fax: +49-202-36-4224; E-mail: hans-martin.siefert.hs{at}bayer.ag.de
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. B. Landersdorfer, M. Kinzig, F. F. Hennig, J. B. Bulitta, U. Holzgrabe, G. L. Drusano, F. Sorgel, and J. Gusinde Penetration of Moxifloxacin into Bone Evaluated by Monte Carlo Simulation Antimicrob. Agents Chemother., May 1, 2009; 53(5): 2074 - 2081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Grayo, M.-C. Lott-Desroches, O. Dussurget, R. Respaud, A. Fontanet, O. Join-Lambert, E. Singlas, and A. Le Monnier Rapid Eradication of Listeria monocytogenes by Moxifloxacin in a Murine Model of Central Nervous System Listeriosis Antimicrob. Agents Chemother., September 1, 2008; 52(9): 3210 - 3215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Grayo, O. Join-Lambert, M. C. Desroches, and A. Le Monnier Comparison of the In Vitro Efficacies of Moxifloxacin and Amoxicillin against Listeria monocytogenes Antimicrob. Agents Chemother., May 1, 2008; 52(5): 1697 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. T. Stearne, A. G. Vonk, B. J. Kullberg, and I. C. Gyssens Effect of Recombinant Murine Granulocyte Colony-Stimulating Factor with or without Fluoroquinolone Therapy on Mixed-Infection Abscesses in Mice Antimicrob. Agents Chemother., September 1, 2005; 49(9): 3668 - 3675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tang and M. Mayersohn ACCURACY OF ALLOMETRICALLY PREDICTED PHARMACOKINETIC PARAMETERS IN HUMANS: ROLE OF SPECIES SELECTION Drug Metab. Dispos., September 1, 2005; 33(9): 1288 - 1293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tang and M. Mayersohn A NOVEL MODEL FOR PREDICTION OF HUMAN DRUG CLEARANCE BY ALLOMETRIC SCALING Drug Metab. Dispos., September 1, 2005; 33(9): 1297 - 1303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. P. Ittner, G. Roth, M. Gruber, M. Pawlik, and K. Taeger Clearance of moxifloxacin during continuous haemofiltration (CVVHF) in vitro J. Antimicrob. Chemother., August 1, 2005; 56(2): 360 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Firsov, I. Y. Lubenko, S. N. Vostrov, Y. A. Portnoy, and S. H. Zinner 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., July 1, 2005; 49(7): 2642 - 2647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kuhl, N. Svenstrup, C. Ladel, M. Otteneder, A. Binas, G. Schiffer, M. Brands, T. Lampe, K. Ziegelbauer, H. Rubsamen-Waigmann, et al. Biological Characterization of Novel Inhibitors of the Gram-Positive DNA Polymerase IIIC Enzyme Antimicrob. Agents Chemother., March 1, 2005; 49(3): 987 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Bast, M. Yue, X. Chen, D. Bell, L. Dresser, R. Saskin, L. A. Mandell, D. E. Low, and J. C. S. de Azavedo Novel Murine Model of Pneumococcal Pneumonia: Use of Temperature as a Measure of Disease Severity To Compare the Efficacies of Moxifloxacin and Levofloxacin Antimicrob. Agents Chemother., September 1, 2004; 48(9): 3343 - 3348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schaumann, R. Blatz, J. Beer, G. Ackermann, and A. C. Rodloff Effect of moxifloxacin versus imipenem/cilastatin treatment on the mortality of mice infected intravenously with different strains of Bacteroides fragilis and Escherichia coli J. Antimicrob. Chemother., February 1, 2004; 53(2): 318 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hayakawa, Y. Fukushima, H. Kato, H. Fukumoto, T. Kadota, H. Yamamoto, H. Kuroiwa, J. Nishigaki, and A. Tsuji METABOLISM AND DISPOSITION OF NOVEL DES-FLUORO QUINOLONE GARENOXACIN IN EXPERIMENTAL ANIMALS AND AN INTERSPECIES SCALING OF PHARMACOKINETIC PARAMETERS Drug Metab. Dispos., November 1, 2003; 31(11): 1409 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Joukhadar, H. Stass, U. Muller-Zellenberg, E. Lackner, F. Kovar, E. Minar, and M. Muller Penetration of Moxifloxacin into Healthy and Inflamed Subcutaneous Adipose Tissues in Humans Antimicrob. Agents Chemother., October 1, 2003; 47(10): 3099 - 3103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Cynamon and M. Sklaney Gatifloxacin and Ethionamide as the Foundation for Therapy of Tuberculosis Antimicrob. Agents Chemother., August 1, 2003; 47(8): 2442 - 2444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Mahmood, M. D. Green, and J. E. Fisher Selection of the First-Time Dose in Humans: Comparison of Different Approaches Based on Interspecies Scaling of Clearance J. Clin. Pharmacol., July 1, 2003; 43(7): 692 - 697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. M. Lenaerts, V. Gruppo, J. V. Brooks, and I. M. Orme Rapid In Vivo Screening of Experimental Drugs for Tuberculosis Using Gamma Interferon Gene-Disrupted Mice Antimicrob. Agents Chemother., February 1, 2003; 47(2): 783 - 785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Lounis, A. Bentoucha, C. Truffot-Pernot, B. Ji, R. J. O'Brien, A. Vernon, G. Roscigno, and J. Grosset Effectiveness of Once-Weekly Rifapentine and Moxifloxacin Regimens against Mycobacterium tuberculosis in Mice Antimicrob. Agents Chemother., December 1, 2001; 45(12): 3482 - 3486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. Bermudez, C. B. Inderlied, P. Kolonoski, M. Petrofsky, P. Aralar, M. Wu, and L. S. Young Activity of Moxifloxacin by Itself and in Combination with Ethambutol, Rifabutin, and Azithromycin In Vitro and In Vivo against Mycobacterium avium Antimicrob. Agents Chemother., January 1, 2001; 45(1): 217 - 222. [Abstract] [Full Text]
|
|