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Antimicrobial Agents and Chemotherapy, February 2004, p. 521-524, Vol. 48, No. 2
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.2.521-524.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics of Total and Unbound Ertapenem in Healthy Elderly Subjects

D. G. Musson,1* A. Majumdar,1 S. Holland,1 K. Birk,1 L. Xi,1 G. Mistry,1 D. Sciberras,1 J. Muckow,2 P. Deutsch,1 and J. D. Rogers1

Merck Research Laboratories, West Point, Pennsylvania 19486,1 Indago, Clinical Research Unit, Staffordshire, England2

Received 25 June 2003/ Returned for modification 29 August 2003/ Accepted 9 November 2003

Ertapenem is a new once-a-day parenteral carbapenem antimicrobial agent. The pharmacokinetics of unbound and total concentrations of ertapenem in plasma were investigated in elderly subjects and compared with historical data from young adults. In a single- and multiple-dose study, healthy elderly males and females (n = 14) 65 years old or older were given a 1-g intravenous (i.v.) dose once daily for 7 days. Plasma and urine samples collected for 24 h on days 1 and 7 following administration of the 1-g doses were analyzed by reversed-phase high-performance liquid chromatography. Areas under the concentration-time curve from 0 h to infinity (AUC0-{infty}) for elderly females and males were similar following administration of 1-g single i.v. doses, and thus, the genders were pooled in subsequent analyses. Concentrations in plasma and the half-life of ertapenem were generally higher and longer, respectively, in elderly subjects than in young adults. The mean AUC0-{infty} of total ertapenem in the elderly was 39% higher than that in young subjects following administration of a 1-g dose. The differences were slightly greater for the mean AUC0-{infty} of unbound ertapenem (71%). The unbound fraction of ertapenem in elderly subjects (~5 to 11%) was generally greater than that in young adults (~5 to 8%). As in young adults, ertapenem did not accumulate upon multiple dosing in the elderly. The pharmacokinetics of ertapenem in elderly subjects, while slightly different from those in young adults, do not require a dosage adjustment for elderly patients.

* Corresponding author. Mailing address: Merck Research Laboratories, Sumneytown Pike, West Point, PA 19486. Phone: (215) 652-8480. Fax: (215) 652-4524. E-mail: don_musson{at}merck.com.

Antimicrobial Agents and Chemotherapy, February 2004, p. 521-524, Vol. 48, No. 2
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.2.521-524.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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