Pharmacokinetics of ertapenem in outpatients with complicated urinary tract infections.

Abstract

OBJECTIVES:

Ertapenem is a broad-spectrum carbapenem antibiotic used to treat severe bacterial infections. In view of its dosing convenience, it is increasingly used as outpatient therapy. The objective of this study was to determine the pharmacokinetics and renal disposition of ertapenem in outpatients with complicated urinary tract infections.

METHODS:

Ertapenem was administered as a daily intravenous infusion of 1 g over 30 min. At steady-state, blood and urine samples were collected over one dosing interval. Drug concentrations in serum and urine were determined using a validated liquid chromatography-tandem mass spectrometry method. A population pharmacokinetic model was used to characterize ertapenem serum and urine profiles. The likelihood of the standard dosing achieving a favourable pharmacokinetic-pharmacodynamic exposure was evaluated using Monte Carlo simulations.

RESULTS:

Ten adult male patients were studied. Concentration-time profiles of ertapenem in both serum (r(2) =0.997) and urine (r(2) =0.982) were captured satisfactorily. Mean values for volume of distribution, clearance and elimination t½ were 4.8 L, 0.7 L/h and 6.1 h, respectively. A high ertapenem concentration (>128 mg/L) could be attained in the urine at 40% of the dosing interval.

CONCLUSIONS:

The pharmacokinetics of ertapenem in serum and urine were characterized. Our simulations suggested that a sufficiently high ertapenem concentration could be achieved in urine to overcome low to intermediate resistance. Clinical investigations to validate our findings are warranted.

• Authors: Jian Zhou, Zuraidah Sulaiman, Ryan M Llorin, Kim-Hor Hee, Lawrence Soon-U Lee, David C Lye, Dale A Fisher, Vincent H Tam
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 69 Issue 9 Pg. 2517-21 (Sep 2014) ISSN: 1460-2091 [Electronic] England
• PMID: 24797063 (Publication Type: Journal Article, Observational Study)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Anti-Bacterial Agents
• beta-Lactams
• Ertapenem

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics)
• Chromatography, Liquid
• Ertapenem
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Models, Statistical
• Outpatients
• Prospective Studies
• Serum (chemistry)
• Tandem Mass Spectrometry
• Urinary Tract Infections (drug therapy)
• Urine (chemistry)
• Young Adult
• beta-Lactams (administration & dosage, pharmacokinetics)