Degree Type

Dissertation

Date of Award

2019

Degree Name

Doctor of Philosophy

Department

Biomedical Sciences

Major

Biomedical Sciences

First Advisor

Jonathan P. Mochel

Abstract

The effects of clinical states of infection on the pharmacokinetics and pharmacodynamics (PK/PD) in ruminant food animal species are not well described. The majority of PK studies utilize healthy animals, and this creates challenges for veterinary professionals treating clinical patients. Knowledge gaps explored are 1) effect of clinical disease on the PK/PD of fentanyl in cattle, 2) effect of pneumonia on the PK/PD of tulathromycin in goats, and 3) the effect of co-administration of ertapenem and an immunomodulator on PK/PD in sheep.

The pharmacokinetics for calves were determined after intravenous dosing of 5 µg/kg fentanyl citrate. The initial PK revealed an increased elimination half-life and mean residence time when compared to other ruminant values. The analytical performance of the assay was extremely sensitive, and as methods become more performant, PK parameters may face the need for adjustment over time.

The PK/PD of fentanyl transdermal patches was determined in healthy and clinical calves. Adverse effects of tachycardia, tachypnea, and hyperthermia were noted in all healthy calves at two variable dosages. Adverse effects were related to the absorption of fentanyl over the initial 4-6 hours, and the absence of acute clinical disease. Clinicians should note that severity of clinical disease may impact PD of fentanyl in calves.

The PK and tissue residue concentration of tulathromycin in goats was determined for healthy (control) and goats with respiratory disease. Volume of distribution was significantly altered by respiratory disease, as well as plasma concentrations. A significantly lower tissue residue concentration was noted in renal tissue from the experimental group. Respiratory disease may alter pharmacokinetics and residues of tulathromycin in meat goats.

Finally the effect P. aeruginosa cystitis and an immunomodulator on the PK/PD of ertapenem was determined for sheep. No significant differences in PK or ertapenem concentration were noted. Significant differences in bactiuria were noted between the control and ertapenem with immunomodulator group. Non-antimicrobial adjunctive therapies such as immunomodulators may present promise as a treatment option for severe infections.

The collective results of this work provide clinicians with evidence regarding the effect of clinical states on the PK/PD in ruminant food animal species. These results can be further elucidated for application of precision therapy in the hospitalized ruminant.

Copyright Owner

Joseph Samuel Smith

Language

en

File Format

application/pdf

File Size

147 pages

Included in

Pharmacology Commons

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