Veterinary Toxicology and Pharmacology Commons^™

Pharmacokinetics Of Single Feeding Of Cannabidiol In Cattle: A Pilot Study, Haley Cornette

Honors College Theses

Cannabidiol (CBD) is a substance that has been used in complementary medicine for many years. However, modern medicine has little knowledge of how this substance is utilized and metabolized in ruminant animals. Regulations on quality assurance and use in animals are lacking, and CBD supplementation in livestock is not approved. If CBD supplements can be shown to be safe and effective, detection in the animal will be important for determining regulation of use. A withdrawal period can then be established to allow time for deterioration of product to safe levels before livestock products enter human markets. This study sought to …

Pharmacokinetics Of Intramuscular Maropitant In Pigs (Sus Scrofa Domesticus), Joseph Smith, Jessica E. Gebert, Lisa S. Ebner, Kailee O. Bennett, Rebecca J. Collins, Chiara E. Hampton, Stephanie A. Kleine, Pierre-Yves Mulon, Christopher K. Smith, Reza Seddighi, Genevieve Bussieres, Jonathan P. Mochel, Healther K. Knych

Faculty Publications and Other Works -- Large Animal Clinical Sciences

Pigs are at risk of vomiting from medical conditions as well as the emetic side effects of drugs administered for peri-operative manipulations, but there is a lack of pharmacokinetic data for potential anti-emetic therapies, such as maropitant, in this species. The main objective of this study was to estimate plasma pharmacokinetic parameters for maropitant in pigs after a single intramuscular (IM) administration dosed at 1.0 mg/ kg. A secondary objective was to estimate pilot pharmacokinetic parameters in pigs after oral (PO) administration at 2.0 mg/kg. Maropitant was administered to six commercial pigs at a dose of 1.0 mg/kg IM. Plasma …

Pharmacokinetics Of Esomeprazole In Goats (Capra Aegagrus Hircus) After Intravenous And Subcutaneous Administration, Rachel L. Fladung, Joseph Smith, Melissa Hines, Windy Soto-Gonzalez, Bryanna Fayne, Rebecca Rahn, Olivia Escher, Lainey Harvill, Joan Bergman, Jessica Garcia, Amanda Kreuder

Faculty Publications and Other Works -- Large Animal Clinical Sciences

Background: Stressed and hospitalized goats are at risk of developing abomasal (gastric) ulceration, but there is a paucity of pharmacokinetic studies for proton pump inhibiting drugs, such as, esomeprazole in goats.

Objectives: The objectives for this study were to estimate plasma pharmacokinetic parameters for esomeprazole in adult goats after intravenous (IV) and subcutaneous (SQ) administration. A secondary objective was to describe the plasma kinetics of the metabolite esomeprazole sulfone after IV and SC administration in goats.

Materials and methods: Esomeprazole was administered to 5 adult goats in a crossover study at doses of 1 mg/kg IV or 2 mg/kg SC. …

Validation Of A Method For Pantoprazole And Its Sulfone Metabolite In Goat Plasma Using High Performance Liquid Chromatography, Sherry Cox, Lainey Harvill, Sarah Bullock, Joseph Smith, Joan Bergman

Faculty Publications and Other Works -- Large Animal Clinical Sciences

No abstract provided.

Gabapentin, A Human Therapeutic Medication And An Environmental Substance Transferring At Trace Levels To Horses: A Case Report., Kimberly Brewer, Jacob Machin, George Maylin, Clara Fenger, Abelardo Morales-Briceño, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Gabapentin, 1-(Aminomethyl)cyclohexaneacetic acid, MW 171.240, is a frequently prescribed high dose human medication that is also used recreationally. Gabapentin is orally absorbed; the dose can be 3,000 mg/day and it is excreted essentially unchanged in urine. Gabapentin is stable in the environment and routinely detected in urban wastewater. Gabapentin randomly transfers from humans to racing horses and is at times detected at pharmacologically ineffective / trace level concentrations in equine plasma and urine. In Ohio racing between January 2019 and July 2020,18 Gabapentin identifications, all less than 2 ng/ml in plasma, were reported. These identifications were ongoing because the horsemen …

Pharmacokinetics Of Butorphanol Following Intravenous And Intramuscular Administration In Donkeys: A Preliminary Study, Lisa S. Ebner, Odette O, Bradley Simon, Ignacio Lizarraga, Joseph Smith, Sherry Cox

Faculty Publications and Other Works -- Large Animal Clinical Sciences

The pharmacokinetics of butorphanol after intravenous (IVB) and intramuscular (IMB) administration in donkeys were determined in this preliminary study. Healthy male gelded donkeys (n = 5), aged 6–12 years old, were administered 0.1 mg/kg butorphanol IV or IM in a randomized, crossover design. Blood samples were obtained at predetermined intervals for 24 h (IVB) and 48 h (IMB) after administration. Plasma butorphanol concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters were calculated. Following IVB administration, mean (± SE) apparent volume of distribution, elimination half-life, total body clearance, and area under the plasma concentration time curve from …

Miniature Companion Pig Sedation And Anesthesia, Joseph Smith, Reza Seddighi

Faculty Publications and Other Works -- Large Animal Clinical Sciences

• Miniature companion pigs (MCP) are increasing in popularity, and as such, there is an increased need for veterinarians trained in sedation and anesthesia for the species.

• MCPs have several species-specific qualities that can complicate injectable drug administration and create challenges for inhalational anesthesia (eg, with endotracheal intubation).

• General anesthetic complications, such as hypothermia and hypotension, are commonly described in miniature companion pigs, so monitoring of vital parameters during anesthetic procedures and recovery is crucial.

Identifying Bisphosphonate Protein Biomarkers In Equine Sera Using Mass Spectrometry Methods, Malinda Jayne Alison Porter

Theses and Dissertations--Veterinary Science

Bone resorptive diseases affect humans and horses, alike. Examples of these diseases include osteoporosis, Paget’s disease, and osteogenesis imperfecta in humans, and navicular disease in the horse (Mitchell et al., 2019; Suva et al., 2021). Bisphosphonates are used to treat these diseases, and may remain in the bone for several years after administration, demonstrating the need for newer drug testing methods.

The purpose of the discovery phase of this study was to use blood samples of in-training horses which had been given an initial administration of the bisphosphonate tiludronate and identify protein biomarkers that changed in response to this class …

Pharmacokinetics Of Orally Administered Prednisolone In Alpacas, Ricardo Videla, Carla Sommardahl, Joseph Smith, Deanna M.W. Schaeffer, Sherry Cox

Faculty Publications and Other Works -- Large Animal Clinical Sciences

This study aimed to determine the pharmacokinetics of prednisolone following intravenous and oral administration in healthy adult alpacas. Healthy adult alpacas were given prednisolone (IV, n = 4), as well as orally (PO, n = 6). Prednisolone was administered IV once (1 mg/kg). Oral administration was once daily for 5 days (2 mg/kg). Each treatment was separated by a minimum 4 month washout period. Samples were collected at 0 (pre-administration), 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, and 24 h after IV administration, and at 0 (pre-administration), 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, 24 after …

Pharmacokinetics Of Pantoprazole And Pantoprazole Sulfone In Goats After Intravenous Administration: A Preliminary Report, Joseph Smith, Jonathan P. Mochel, Windy M. Soto-Gonzalez, Rebecca R. Rahn, Bryanna M. Fayne, Olivia G. Escher, Anastasia M. Geletka, Lainey E. Harvill, Joan B. Bergman, Sherry Cox

Faculty Publications and Other Works -- Large Animal Clinical Sciences

Background: Ruminant species are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for anti-ulcer therapies, such as the proton pump inhibitor pantoprazole, in goats.

Objective: The primary study objective was to estimate the plasma pharmacokinetic parameters for pantoprazole in adult goats after intravenous administration. A secondary objective was to describe the pharmacokinetic parameters for the metabolite, pantoprazole sulfone, in goats.

Methods: Pantoprazole was administered intravenously to six adult goats at a dose of 1 mg/kg. Plasma samples were collected over 36h and analyzed via reverse phase high performance liquid chromatography for determination of pantoprazole …

Pharmacokinetics Of Tulathromycin In Pregnant Ewes (Ovis Aries) Challenged With Campylobacter Jejuni, Michael Yaeger, Jonathan P. Mochel, Zuowei Wu, Paul Plummer, Orhan Sahin, Joseph Smith, Melda Ocal, Ashenafi Beyi, Changyun Xu, Qijing Zhang, Ronald W. Griffith

Faculty Publications and Other Works -- Large Animal Clinical Sciences

The purpose of this study was to evaluate the pharmacokinetics of tulathromycin in the plasma and maternal and fetal tissues of pregnant ewes when administered within 24 hours of a single, IV Campylobacter jejuni (C. jejuni) challenge. Twelve, pregnant ewes between 72–92 days of gestation were challenged IV with C. jejuni IA3902 and then treated with 1.1 ml/45.36 kg of tulathromycin subcutaneously 18 hours post-challenge. Ewes were bled at predetermined time points and euthanized either at a predetermined time point or following the observation of vaginal bleeding or abortion. Following euthanasia, tissues were collected for bacterial …

Nonlinear Mixed-Effect Pharmacokinetic Modeling And Distribution Of Doxycycline In Healthy Female Donkeys After Multiple Intragastric Dosing–Preliminary Investigation, Ronan J.J. Chapuis, Joseph Smith, Hilari M. French, Felix Ngosa Toka, Erik W. Peterson, Erika L. Little

Faculty Publications and Other Works -- Large Animal Clinical Sciences

Doxycycline (DXC) is a broad-spectrum antibacterial antimicrobial administered to horses for the treatment of bacterial infections which may also affect donkeys. Donkeys have a different metabolism than horses, leading to differences in the pharmacokinetics of drugs compared to horses. This study aimed to describe the population pharmacokinetics of DXC in donkeys. Five doses of DXC hyclate (10 mg/kg) were administered via a nasogastric tube, q12 h, to eight non-fasted, healthy, adult jennies. Serum, urine, synovial fluid and endometrium were collected for 72 h following the first administration. Doxycycline concentration was measured by competitive enzyme immunoassay. Serum concentrations versus time data …

Compounded Gabapentin For Felines: Associated Metabolic Processes And Analysis Of Potency, Johnny Altwal

Student Scholar Symposium Abstracts and Posters

Pharmaceutical compounding provides pharmacists and clinicians the opportunity to create unique drug formulations that are better suited to a specific patient’s needs. This is especially prevalent in veterinary medicine where clinicians treat a variety of maladies in a large number of species, thereby requiring unique formulations to more easily deliver drugs to animals. Several examples of compounded veterinary formulations with sub-therapeutic potencies have been published, but none examine compounded gabapentin. Gabapentin is frequently compounded into an oral suspension for veterinary use from tablets or capsules for the purpose of pain management in felines and other small animals. The project’s goals …

Case Report: Successful Management Of Refractory Keratomycosis In An Alpaca Using Penetrating Keratoplasty And Combination Antifungal Therapy (Caspofungin 0.5% And Terbinafine 1%), Braidee C. Foote, Joseph Smith, Anna Catherine Bowden, Rachel A. Allbaugh, Lionel Sebbag

Faculty Publications and Other Works -- Large Animal Clinical Sciences

Fungal keratitis is a common disease in certain parts of the world and affects several species, including equids, camelids, and homo sapiens, leading to blindness or loss of the eye if the infection is not adequately controlled. Reports of clinical use of antifungals caspofungin and terbinafine are limited across both veterinary and human medical literature. The alpaca presented in this case demonstrates that deep keratomycosis can be caused by Scopulariopsis brevicaulis and Fusarium verticillioides, two previously unreported fungi to cause keratomycosis in camelids. This report demonstrates successful management with a combination of surgery and topical ophthalmic treatment with caspofungin …

Science-Based Regulation Of Pharmacological Substances In Competition Horses, Jacob Machin

Theses and Dissertations--Toxicology and Cancer Biology

Current testing methodologies within equine forensic toxicology focus on arbitrary thresholds and zero-tolerance policy. Modern analytical chemistry’s limits of detection are low enough that oftentimes femtogram-per-milliliter amounts of a substance can readily be identified in both blood and urine of a horse. For most pharmacologically relevant compounds, these concentrations have no relevance to pharmacological effect. It is therefore crucial that testing methodologies to determine appropriate thresholds and cut-offs be developed that are driven by biological activity rather than arbitrary limits of detection. This dissertation looks to address this by suggesting a system of calculated Effective Plasma Concentrations by which a …

The Comparative Cytotoxicity Of Riddelliine In Primary Mouse, Rat And Chick Hepatocytes, Bryan L. Stegelmeier, William S. Resager, Steven M. Colegate

Poisonous Plant Research (PPR)

Dehydropyrrolizidine alkaloid (DHPA) producing plants commonly poison livestock, wildlife and humans. Poisoning occurs when DHPAs are ingested as feed or food, or when they contaminate medicinal or herbal products. Direct toxicologic comparison of individual DHPAs is essential to estimate their actual health risks. This has been problematic due to varying models and difficulties in DHPA isolation or synthesis. In contrast, the macrocyclic DHPA riddelliine is readily isolated and it has been used as a benchmark to characterize different models of toxicity and carcinogenicity. Following earlier work with immortalized cell lines, the objective of this study was to characterize the effect …

Dynamics Of Larkspur (Delphinium Barbeyi) Pellet Consumption And Tolerance Of The Inhibitory Effects Of Larkspur Alkaloids On Muscle Function In Cattle., Benedict T. Green, Jim Pfister, Dale Gardner, Kevin Welch, Daniel Cook

Poisonous Plant Research (PPR)

Larkspurs (Delphinium spp.) are toxic native plants on foothill and mountain rangelands in western North America, which poison cattle grazing on those rangelands. The purpose of this study was to examine in a laboratory setting, the subclinical effects of larkspur intake and toxicosis, by allowing larkspur susceptible and resistant cattle to self-select the amount of larkspur consumed in pellet form. We hypothesized that there would be differences in short term (9 – 11 day) pellet consumption between susceptible and resistant animals. Two trials were completed, each with larkspur resistant and susceptible Angus steers, and larkspur-alfalfa pellets at a 12% …

North American Hard Yellow Liver Disease: An Old Problem Readdressed, Bryan L. Stegelmeier, Meredyth Jones, Christopher P. Womack, T Zane Davis, Dale R. Gardner

Poisonous Plant Research (PPR)

Hard yellow liver disease or fatty cirrhosis periodically affects cattle, sheep, goats, pronghorn antelope (Antilocapra americana) and whitetail deer (Odocoileus virginianus texanus) within several Texas counties in the United States. Clinically it presents as chronic liver disease with progressive hepatic necrosis and fibrosis, icterus and liver failure. The damaged livers are yellow and many have multiple firm, often gritty foci that are scattered throughout all lobes. Early investigations included feeding studies using potential toxic plants, climate and forage studies, infectious disease surveys and various mycotoxin studies and analyses. None have definitively reproduced the disease or identified the inciting …

Physiological And Behavioural Evaluation Of Common Anaesthesia Practices In The Rainbow Trout, Kieran C. Pounder, Jennifer L. Mitchell, Jack S. Thomson, Tom G. Pottinger, Lynne U. Sneddon

Lynne Sneddon, PhD

Anaesthetic drugs are commonly administered to fish in aquaculture, research and veterinary contexts. Anaesthesia causes temporary absence of consciousness and may reduce the stress and/or pain associated with handling and certain invasive procedures. The rainbow trout (Oncorhynchus mykiss) is a widely-used model species with relevance to both aquaculture and natural ecosystems. This study sought to establish the relative acute impact of commonly used anaesthetics on rainbow trout when used for anaesthesia or euthanasia by exploring their effects on aversion behaviour and stress physiology. Five widely used anaesthetics were investigated at two concentrations reflective of common laboratory practises: MS-222, benzocaine, 2-phenoxyethanol, …

Reduction In Activity By Noxious Chemical Stimulation Is Ameliorated By Immersion In Analgesic Drugs In Zebrafish, Javier Lopez-Luna, Qussay Al-Jubouri, Waleed Al-Nuaimy, Lynne U. Sneddon

Lynne Sneddon, PhD

Research has recently demonstrated that larval zebrafish show similar molecular responses to nociception to those of adults. Our study explored whether unprotected larval zebrafish exhibited altered behaviour after exposure to noxious chemicals and screened a range of analgesic drugs to determine their efficacy to reduce these responses. This approach aimed to validate larval zebrafish as a reliable replacement for adults as well as providing a high-throughput means of analysing behavioural responses. Zebrafish at 5 days postfertilization were exposed to known noxious stimuli: acetic acid (0.01%, 0.1% and 0.25%) and citric acid (0.1%, 1% and 5%). The behavioural response of each …