Campus Units

Veterinary Diagnostic and Production Animal Medicine, Veterinary Microbiology and Preventive Medicine, Biomedical Sciences

Document Type

Article

Publication Version

Published Version

Publication Date

10-2019

Journal or Book Title

Comparative Medicine

Volume

69

Issue

5

First Page

413

Last Page

418

DOI

10.30802/AALAS-CM-18-000144

Abstract

Sheep are commonly used as animal models for human biomedical research, but descriptions of their use for studying the pharmacokinetics of carbapenem antimicrobials, such as ertapenem, are unavailable. Ertapenem is a critical antimicrobial for human infections, and the description of the pharmacokinetics of this drug is of value for research using ovine as models for human diseases, such as urinary tract infections (UTI). There are currently no ovine models for comparative biomedical research of UTI. The objective of this study was to report the pharmacokinetics of ertapenem in sheep after single and multiple dosing. In addition, we explored the effects of an immunomodulatory drug (Zelnate) on the pharmacokinetics of ertapenem in sheep. Eight healthy ewes (weight, 64.4 ± 7.7 kg) were used in an ovine bacterial cystitis model of human cystitis with Pseudomonas aeruginosa. After disease confirmation, each ewe received 1 g of ertapenem intravenously once every 24 h for 5 administrations. Blood was collected intensively (14 samples) during 24 h after the first and last administration. After multiple-dose administration, the volume of distribution was 84.5 mL/kg, clearance was 116.3 mL/h/kg, T1/2(λz) was 1.1 h, and the extraction ratio was 0.02. No significant differences in pharmacokinetic parameters or time points were found between groups treated with the immunostimulant and controls or after the 1st or 5th administration of ertapenem. No accumulation was noted from previous administration. Our ovine pharmacokinetic findings can be used to evaluate therapeutic strategies for ertapenem use (varying drug dosing schedules and combinations with other antimicrobials or immune modulators) in the context of UTI.

Comments

This article is published as Smith, Joe S., David J. Borts, Clare C. Slagel, Suzanne M. Rajewski, Alain Bousquet-Melou, Aude A. Ferran, Paul J. Plummer, and Jon P. Mochel. "Pharmacokinetics of Ertapenem in Sheep (Ovis aries) with Experimentally Induced Urinary Tract Infection." Comparative Medicine 69, no. 5 (2019): 413-418. DOI: 10.30802/AALAS-CM-18-000144. Posted with permission.

Copyright Owner

American Association for Laboratory Animal Science

Language

en

File Format

application/pdf

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