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Antimicrobial Agents and Chemotherapy, November 2002, p. 3506-3511, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3506-3511.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics of Ertapenem in Healthy Young Volunteers

A. K. Majumdar,1* D. G. Musson,1 K. L. Birk,1 C. J. Kitchen,1 S. Holland,1 J. McCrea,1 G. Mistry,1 M. Hesney,1 L. Xi,1 S. X. Li,1 R. Haesen,1 R. A. Blum,2 R. L. Lins,3 H. Greenberg,4 S. Waldman,4 P. Deutsch,1 and J. D. Rogers1

Merck Research Laboratories, West Point,1 Thomas Jefferson University Hospital, Philadelphia, Pennsylvania,4 Millard Filmore Hospital, Buffalo, New York,2 SGS Biopharma Research Unit Stuivenberg, Antwerp, Belgium3

Received 7 February 2002/ Returned for modification 11 May 2002/ Accepted 25 July 2002

Ertapenem (INVANZ) is a new once-a-day parenteral ß-lactam antimicrobial shown to be effective as a single agent for treatment of various community-acquired and mixed infections. The single- and multiple-dose pharmacokinetics of ertapenem at doses up to 3 g were examined in healthy young men and women volunteers. Plasma and urine samples collected were analyzed using reversed-phase high-performance liquid chromatography with UV detection. Ertapenem is highly bound to plasma protein. The protein binding changes from ~95% bound at concentrations of <50 µg/ml to ~92% bound at concentrations of 150 µg/ml (concentration at the end of a 30-min infusion following the 1-g dose). The nonlinear protein binding of ertapenem resulted in a slightly less than dose proportional increase in the area under the curve from 0 h to infinity (AUC0-{infty}) of total ertapenem. The single-dose AUC0-{infty} of unbound ertapenem was nearly dose proportional over the dose range of 0.5 to 2 g. The mean concentration of ertapenem in plasma ranged from ~145 to 175 µg/ml at the end of a 30-min infusion, from ~30 to 34 µg/ml at 6 h, and from ~9 to 11 µg/ml at 12 h. The mean plasma t1/2 ranged from 3.8 to 4.4 h. About 45% of the plasma clearance (CLP) was via renal clearance. The remainder of the CLP was primarily via the formation of the ß-lactam ring-opened metabolite that was excreted in urine. There were no clinically significant differences between the pharmacokinetics of ertapenem in men and women. Ertapenem does not accumulate after multiple once-daily dosing.

* Corresponding author. Mailing address: WP75-200, Merck Research Laboratories West Point, PA 19486. Phone: (215) 652-0761. Fax: (215) 993-1335. E-mail: anup_majumdar{at}Merck.com.

Antimicrobial Agents and Chemotherapy, November 2002, p. 3506-3511, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3506-3511.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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