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Antimicrobial Agents and Chemotherapy, October 2004, p. 3765-3772, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3765-3772.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Ertapenem Pharmacokinetics and Impact on Intestinal Microflora, in Comparison to Those of Ceftriaxone, after Multiple Dosing in Male and Female Volunteers

Mathias W. R. Pletz,1* Mareike Rau,1 Juergen Bulitta,2 Andres De Roux,1 Olaf Burkhardt,1 Guido Kruse,3 Michael Kurowski,3 Carl E. Nord,4 and Hartmut Lode1

Department of Chest and Infectious Diseases, City Hospital Emil von Behring/Chest Hospital Heckeshorn, Freie Universität Berlin,1 Department of Laboratory Medicine, Auguste Viktoria Hospital Berlin,3 Institute for Biomedical and Pharmaceutical Research, Nuernberg-Heroldsberg Germany,2 Department of Laboratory Medicine, Division of Clinical Bacteriology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden4

Received 26 February 2004/ Returned for modification 24 April 2004/ Accepted 9 June 2004

The pharmacokinetics of ertapenem and ceftriaxone were investigated in an open, randomized, two-period crossover study after single- and multiple-dose administration in 10 healthy volunteers (five women and five men). Both antibiotics were administered intravenously once daily for 7 days at dosages of 1 g (ertapenem) and 2 g (ceftriaxone). The concentrations of the antibiotics in serum and urine were quantified by the agar well diffusion method bioassay and, in addition, for ertapenem only, by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). For ertapenem the maximum concentration of the drug in plasma (Cmax) was 256 mg/liter, the half-life was 20.7 h, and the area under the plasma concentration-time curve (AUC) was 830 mg · h/liter. The concentrations in fecal samples were (mean value) 37.2 and 32.7 mg/kg on day 4 and day 8, respectively. Ceftriaxone exhibited a mean Cmax of 315 mg/liter, a half-life of 7.6 h, and an AUC of 1,556 mg · h/liter. The mean concentrations in fecal samples were 153 and 258 mg/kg on day 4 and day 8, respectively. No accumulation of ertapenem or ceftriaxone was detected at steady state. A slightly but significantly decreased AUC for ertapenem was detected for the female volunteers. No serious adverse event was observed. Both antibiotics induced a marked decrease in the anaerobic microflora (4-log-unit decreases in lactobacilli, bifidobacteria, clostridia, and bacteroides) and Escherichia coli, whereas the number of enterococci increased (4 log units). A slight overgrowth of yeasts was observed with both regimens. In all cases the microflora returned to normal levels on days 21 to 35.

* Corresponding author. Present address: Department of International Health, Rollins School of Public Health, Emory University, 1518 Clifton Rd., Atlanta, GA 30322. Phone: (404) 727-3984. Fax: (404) 712-8419. E-mail: mpletz{at}sph.emory.edu.

Antimicrobial Agents and Chemotherapy, October 2004, p. 3765-3772, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3765-3772.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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