This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krueger, W. A. Articles by Sörgel, F. Search for Related Content PubMed PubMed Citation Articles by Krueger, W. A. Articles by Sörgel, F.

Evaluation by Monte Carlo Simulation of the Pharmacokinetics of Two Doses of Meropenem Administered Intermittently or as a Continuous Infusion in Healthy Volunteers

IBMP—Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg, Germany,¹ Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Tübingen, Germany,² Pharmaceutical Chemistry, University of Würzburg, Würzburg, Germany,³ Department of Urology, St. Elisabeth Hospital, Straubing, Germany,⁴ Ordway Research Institute, Inc., Albany, New York 12208⁵

Received 8 August 2004/ Returned for modification 17 November 2004/ Accepted 3 February 2005

Meropenem is a broad-spectrum carbapenem antibacterial agent. In order to optimize levels in plasma relative to the MICs, the ideal dose level and dosage regimen need to be determined. The pharmacokinetics of meropenem were studied in two groups, each comprising eight healthy volunteers who received the following doses: 500 mg as an intravenous infusion over 30 min three times a day (t.i.d.) versus a 250-mg loading dose followed by a 1,500 mg continuous infusion over 24 h for group A and 1,000 mg as an intravenous infusion over 30 min t.i.d. versus a 500-mg loading dose followed by a 3,000-mg continuous infusion over 24 h for group B. Meropenem concentrations in plasma and urine were determined by liquid chromatography-mass spectrometry/mass spectrometry and high-performance liquid chromatography with UV detection, respectively. Pharmacokinetic calculations were done by use of a two-compartment open model, and the data were extrapolated by Monte Carlo simulations for 10,000 simulated subjects for pharmacodynamic evaluation. There were no significant differences in total clearance and renal clearance between group A and group B or between the intermittent treatment and the continuous infusion. The analyses of the probability of target attainment by MIC for the high- and low-dose continuous infusions were robust up to MICs of 4 mg/liter and 2 mg/liter, respectively. The corresponding values for intermittent infusions were only 0.5 mg/liter and 0.25 mg/liter. When these observations were correlated with MICs obtained from the MYSTIC database, intermittent infusion results in adequate activity against two of the most common nosocomially acquired pathogens, Klebsiella pneumoniae and Enterobacter cloacae. However, against Pseudomonas aeruginosa, the evaluation shows a clear advantage of high-dose therapy administered as a continuous infusion. We believe that in the empirical therapy situation, the continuous-infusion mode of administration is most worth the extra efforts. We conclude that clinical trials for evaluation of the continuous infusions of meropenem in critically ill patients are warranted.

This article has been cited by other articles:

• Krueger, W. A., Kempf, V. A. J., Peiffer, M., Nagele, U., Unertl, K. E., Schroeder, T. H. (2008). Treatment with Tigecycline of Recurrent Urosepsis Caused by Extended-Spectrum-{beta}-Lactamase-Producing Escherichia coli. J. Clin. Microbiol. 46: 817-820 [Abstract] [Full Text]  
• Henrichfreise, B., Wiegand, I., Luhmer-Becker, I., Wiedemann, B. (2007). Development of Resistance in Wild-Type and Hypermutable Pseudomonas aeruginosa Strains Exposed to Clinical Pharmacokinetic Profiles of Meropenem and Ceftazidime Simulated In Vitro. Antimicrob. Agents Chemother. 51: 3642-3649 [Abstract] [Full Text]  
• Li, C., Kuti, J. L., Nightingale, C. H., Nicolau, D. P. (2006). Population pharmacokinetic analysis and dosing regimen optimization of meropenem in adult patients.. J Clin Pharmacol 46: 1171-1178 [Abstract] [Full Text]  
• Lorente, L., Lorenzo, L., Martin, M. M, Jimenez, A., Mora, M. L (2006). Meropenem by Continuous Versus Intermittent Infusion in Ventilator-Associated Pneumonia due to Gram-Negative Bacilli. The Annals of Pharmacotherapy 40: 219-223 [Abstract] [Full Text]