Pharmacokinetics of Ertapenem in Sheep (Ovis aries) with Experimentally Induced Urinary Tract Infection

dc.contributor.author Plummer, Paul
dc.contributor.author Smith, Joe
dc.contributor.author Smith, Joe
dc.contributor.author Borts, David
dc.contributor.author Slagel, Clare
dc.contributor.author Rajewski, Suzanne
dc.contributor.author Mochel, Jonathan
dc.contributor.author Bousquet‑Melou, Alain
dc.contributor.author Ferran, Aude
dc.contributor.author Plummer, Paul
dc.contributor.author Mochel, Jonathan
dc.contributor.department Biomedical Sciences
dc.contributor.department Veterinary Microbiology and Preventive Medicine
dc.contributor.department Veterinary Diagnostic and Production Animal Medicine
dc.date 2019-10-25T19:19:17.000
dc.date.accessioned 2020-07-07T05:12:59Z
dc.date.available 2020-07-07T05:12:59Z
dc.date.copyright Tue Jan 01 00:00:00 UTC 2019
dc.date.issued 2019-10-01
dc.description.abstract <p>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 <em>Pseudomonas aeruginosa</em>. 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.</p>
dc.description.comments <p>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 (<em>Ovis aries</em>) with Experimentally Induced Urinary Tract Infection." <em>Comparative Medicine</em> 69, no. 5 (2019): 413-418. DOI: <a href="http://dx.doi.org/10.30802/AALAS-CM-18-000144" target="_blank">10.30802/AALAS-CM-18-000144</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/vdpam_pubs/160/
dc.identifier.articleid 1164
dc.identifier.contextkey 15623880
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath vdpam_pubs/160
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/92005
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/vdpam_pubs/160/0-2019_SmithJoe_PermGrant_AALAS.pdf|||Fri Jan 14 20:53:43 UTC 2022
dc.source.bitstream archive/lib.dr.iastate.edu/vdpam_pubs/160/2019_SmithJoe_PharmacokineticsErtapenem.pdf|||Fri Jan 14 20:53:45 UTC 2022
dc.source.uri 10.30802/AALAS-CM-18-000144
dc.subject.disciplines Large or Food Animal and Equine Medicine
dc.subject.disciplines Veterinary Infectious Diseases
dc.title Pharmacokinetics of Ertapenem in Sheep (Ovis aries) with Experimentally Induced Urinary Tract Infection
dc.type article
dc.type.genre article
dspace.entity.type Publication
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