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
Services
Right arrow Similar articles in this journal
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 Montgomery, M. J.
Right arrow Articles by Gill, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Montgomery, M. J.
Right arrow Articles by Gill, M. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, December 2001, p. 3468-3473, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3468-3473.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Population Pharmacokinetics and Use of Monte Carlo Simulation To Evaluate Currently Recommended Dosing Regimens of Ciprofloxacin in Adult Patients with Cystic Fibrosis

Megan J. Montgomery,1 Paul M. Beringer,1,* Amir Aminimanizani,1 Stan G. Louie,1,2 Bertrand J. Shapiro,2 Roger Jelliffe,2 and Mark A. Gill1

School of Pharmacy1 and School of Medicine,2 University of Southern California, Los Angeles, California

Received 30 March 2001/Returned for modification 15 July 2001/Accepted 20 September 2001

Pharmacodynamic data on ciprofloxacin indicate that a target area under the concentration-time curve from 0 to 24 h (AUC0-24)/MIC ratio of >= 125 is necessary to achieve optimal bactericidal activity for the treatment of gram-negative pneumonia. The purpose of this prospective study was to (i) develop a pharmacokinetic (PK) model to be utilized for therapeutic drug monitoring (TDM) of ciprofloxacin and (ii) evaluate current ciprofloxacin dosing regimens for pneumonias in cystic fibrosis (CF) patients. Twelve adult CF patients received a single 400-mg dose of IV ciprofloxacin. Six blood samples were obtained over a 12-h interval. Serum drug concentrations were determined by high-pressure liquid chromotography and were fitted to one- and two-compartment models by using NPEM2. Ciprofloxacin MIC data for Pseudomonas aeruginosa were obtained from 1,213 CF patients enrolled in a large clinical trial. A Monte Carlo simulation was performed to estimate the fractional attainment of an AUC0-24/MIC ratio of >= 125. A two-compartment model best describes the serum drug concentration data. The mean fitted PK parameter values are volume of distribution in the central compartment, 0.29 liter/kg; volume of distribution at steady state, 1.1 liters/kg; total clearance, 0.34 liter/h/kg; distributional clearance, 0.89 liter/h/kg; half-life at alpha  phase, 0.16 h; and half-life at beta  phase, 2.9 h. The overall fractional attainment of achieving an AUC0-24/MIC ratio of >= 125 against P. aeruginosa isolates with ciprofloxacin (400 mg every 12 h [q12h] and 8 qh) were 10 and 30%, respectively. A clinical breakpoint MIC of <0.5 µg/ml for susceptibility is suggested, based on an examination of the fractional attainment of the AUC0-24/MIC target at each MIC. The recommended doses of 400 mg q8h or q12h may be inadequate to treat an acute pulmonary exacerbation when given alone. The poor and variable AUC0-24/MIC ratios support the use of TDM to monitor and adjust the dosage to optimize the efficacy of ciprofloxacin therapy in these patients.

* Corresponding author. Mailing address: School of Pharmacy, USC, 1985 Zonal Ave., Los Angeles, CA 90089-9121. Phone: (323) 442-1402. Fax: (626) 628-3024. E-mail: beringer{at}usc.edu.

Antimicrobial Agents and Chemotherapy, December 2001, p. 3468-3473, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3468-3473.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Grayo, S., Lott-Desroches, M.-C., Dussurget, O., Respaud, R., Fontanet, A., Join-Lambert, O., Singlas, E., Le Monnier, A. (2008). Rapid Eradication of Listeria monocytogenes by Moxifloxacin in a Murine Model of Central Nervous System Listeriosis. Antimicrob. Agents Chemother. 52: 3210-3215 [Abstract] [Full Text]  
  • Rodriguez-Tudela, J. L., Almirante, B., Rodriguez-Pardo, D., Laguna, F., Donnelly, J. P., Mouton, J. W., Pahissa, A., Cuenca-Estrella, M. (2007). Correlation of the MIC and Dose/MIC Ratio of Fluconazole to the Therapeutic Response of Patients with Mucosal Candidiasis and Candidemia. Antimicrob. Agents Chemother. 51: 3599-3604 [Abstract] [Full Text]  
  • Vinks, A. A., van Rossem, R. N., Mathot, R. A. A., Heijerman, H. G. M., Mouton, J. W. (2007). Pharmacokinetics of Aztreonam in Healthy Subjects and Patients with Cystic Fibrosis and Evaluation of Dose-Exposure Relationships Using Monte Carlo Simulation. Antimicrob. Agents Chemother. 51: 3049-3055 [Abstract] [Full Text]  
  • Zelenitsky, S., Ariano, R., Harding, G., Forrest, A. (2005). Evaluating Ciprofloxacin Dosing for Pseudomonas aeruginosa Infection by Using Clinical Outcome-Based Monte Carlo Simulations. Antimicrob. Agents Chemother. 49: 4009-4014 [Abstract] [Full Text]  
  • Dupont, P., Hocquet, D., Jeannot, K., Chavanet, P., Plesiat, P. (2005). Bacteriostatic and bactericidal activities of eight fluoroquinolones against MexAB-OprM-overproducing clinical strains of Pseudomonas aeruginosa. J Antimicrob Chemother 55: 518-522 [Abstract] [Full Text]  
  • Regoes, R. R., Wiuff, C., Zappala, R. M., Garner, K. N., Baquero, F., Levin, B. R. (2004). Pharmacodynamic Functions: a Multiparameter Approach to the Design of Antibiotic Treatment Regimens. Antimicrob. Agents Chemother. 48: 3670-3676 [Abstract] [Full Text]  
  • Mouton, J. W., Schmitt-Hoffmann, A., Shapiro, S., Nashed, N., Punt, N. C. (2004). Use of Monte Carlo Simulations To Select Therapeutic Doses and Provisional Breakpoints of BAL9141. Antimicrob. Agents Chemother. 48: 1713-1718 [Abstract] [Full Text]  
  • Jorgensen, J. H. (2004). Need for Susceptibility Testing Guidelines for Fastidious or Less-Frequently Isolated Bacteria. J. Clin. Microbiol. 42: 493-496 [Full Text]  
  • Payen, S., Serreau, R., Munck, A., Aujard, Y., Aigrain, Y., Bressolle, F., Jacqz-Aigrain, E. (2003). Population Pharmacokinetics of Ciprofloxacin in Pediatric and Adolescent Patients with Acute Infections. Antimicrob. Agents Chemother. 47: 3170-3178 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»