@article{wiloch_enomoto_smith_baynes_messenger_2024, title={Pharmacokinetics of intranasal and intramuscular flunixin in healthy grower pigs}, volume={1}, ISSN={["1365-2885"]}, url={https://doi.org/10.1111/jvp.13426}, DOI={10.1111/jvp.13426}, abstractNote={AbstractFlunixin meglumine is a nonsteroidal anti‐inflammatory drug approved to manage pyrexia associated with swine respiratory disease. In the United States, no analgesic drugs are approved for use in swine by the FDA, although they are needed to manage painful conditions. This study evaluated the pharmacokinetics and relative bioavailability of intranasal versus intramuscular flunixin in grower pigs. Six pigs received 2.2 mg/kg flunixin either intranasally via atomizer or intramuscularly before receiving flunixin via the opposite route following a 5‐day washout period. Plasma samples were collected over 60 h and analysed using ultra‐performance liquid chromatography and tandem mass spectrometry to detect flunixin plasma concentrations. A non‐compartmental pharmacokinetic analysis was performed. The median Cmax was 4.0 μg/mL and 2.7 μg/mL for intramuscular and intranasal administration, respectively, while the median AUCinf was 6.9 h μg/mL for intramuscular administration and 4.9 h μg/mL for intranasal administration. For both routes, the median Tmax was 0.2 h, and flunixin was detectable in some samples up to 60 h post‐administration. Intranasal delivery had a relative bioavailability of 88.5%. These results suggest that intranasal flunixin has similar, although variable, pharmacokinetic parameters to the intramuscular route, making it a viable route of administration for use in grower swine.}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Wiloch, Emily E. and Enomoto, Hiroko and Smith, Lilly and Baynes, Ronald E. and Messenger, Kristen M.}, year={2024}, month={Jan} }
 @article{enomoto_elliot_petritz_crespo_yeatts_sheela_fricke_singleton_thomson_baynes_2024, title={Residue, distribution and depletion of fluralaner in egg following a single intravenous and transdermal administration in healthy shaver hens: fluralaner residue in egg}, volume={103}, ISSN={["1525-3171"]}, url={https://doi.org/10.1016/j.psj.2024.103843}, DOI={10.1016/j.psj.2024.103843}, abstractNote={The demand for the use of fluralaner in an extra label manner is increasing due to lack of efficacious treatment to combat mites and bed bugs in the poultry industry in the United States. Fluralaner residue data in eggs is lacking and residues might cause risks to human health. The present study aimed to determine the depletion profiles of fluralaner in eggs and estimate the drug withdrawal interval in whole eggs by adopting the US Food and Drug administration tolerance limit method with single intravenous (0.5 mg/kg) or transdermal administration (average 58.7 mg/kg) in healthy shaver hens. Hens were treated intravenously or trans-dermally with fluralaner. The eggs were collected daily for 28 days for intravenous treated and for 40 days from the transdermal route group. Fluralaner concentrations in yolk and albumen were determined by mass spectrometry. The greater percentage of fluralaner was observed in yolk when compared to the albumen for both administration routes. Non-compartmental analysis was used to calculate the pharmacokinetic parameters in yolk, albumen and whole egg. The longest apparent half-life confirmed in yolk was 3.7 days for intravenous and 14.3 days for the transdermal route. The withdrawal intervals in whole egg for fluralaner following the intravenous and transdermal administration were 7 days and 81 days, respectively, with maximum residue limits (1.3 µg/g) at 13 days and 171 days, respectively, based on the limit of quantification (0.4 µg/g) from the analytical assay reported by EMA and APVMA.}, number={7}, journal={POULTRY SCIENCE}, author={Enomoto, Hiroko and Elliot, Baxter A. and Petritz, Olivia A. and Crespo, Rocio and Yeatts, James and Sheela, Farha Ferdous and Fricke, Isabel and Singleton, Abby and Thomson, Andrea and Baynes, Ronald E.}, year={2024}, month={Jul} }
 @article{petritz_enomoto_meyer_thomson_baynes_flammer_2023, title={Pharmacokinetics and Safety of Sulfamethoxazole-Trimethoprim After Oral Administration of Single and Multiple Doses to Rhode Island Red Chickens (<i>Gallus gallus domesticus</i>)}, volume={37}, ISSN={["1938-2871"]}, DOI={10.1647/22-00020}, abstractNote={Abstract: Sulfamethoxazole-trimethoprim (SMZ-TMP), a commonly prescribed antibiotic for backyard hens, is neither Food and Drug Administration approved nor prohibited in laying hens in the United States. The aim of this study was to determine whether plasma concentrations above targeted minimum inhibitory concentration breakpoint values for Enterobacteriaceae could be achieved with oral dosing. Five Rhode Island red hens (Gallus gallus domesticus) were administered a single dose of 96 mg/kg SMZ-TMP (80 mg/kg SMZ and 16 mg/kg TMP) IV followed by the same dose orally after a washout period. Following oral dosing, mean SMZ concentrations exceeded the target breakpoint for approximately 12 hours; however, TMP only briefly exceeded the target breakpoint. Bioavailability was 60.5% for SMZ and 82.0% for TMP. Ten naïve birds were allocated into control (n = 4) and treatment (n = 6) groups for a 7-day multi-dose study. Treatment birds received an oral suspension dosed at 16 mg/kg TMP and 80 mg/kg SMZ every 48 hours (on days 1, 3, 5, and 7); TMP tablets were additionally dosed at 25 mg/bird on days 1, 3, 5, and 7, and 50 mg/bird on days 2, 4, and 6. Plasma SMZ-TMP concentrations were measured on a multiple time interval by ultraperformance liquid chromatography–mass spectrometry, and pharmacokinetic analyses were performed using a noncompartmental model. No accumulation for either drug was noted following repeated dosing, and no statistical differences in biochemical values, packed cell volumes, or weight were found between pre- and posttreatment in either the treatment or control groups. Sulfamethoxazole (80 mg/kg q48h PO) and TMP (24.1–28.0 mg/kg q24h PO) maintained therapeutic plasma concentrations at or exceeding the minimum inhibitory concentration breakpoint of Enterobacteriaceae for 72 and 24 hours for TMP and SMZ, respectively, without evidence of adverse effects or drug accumulation. Further studies are needed to refine this dosage regimen and evaluate adverse effects in ill birds.}, number={1}, journal={JOURNAL OF AVIAN MEDICINE AND SURGERY}, author={Petritz, Olivia A. and Enomoto, Hiroko and Meyer, Emma G. and Thomson, Andrea and Baynes, Ronald E. and Flammer, Keven}, year={2023}, month={Mar}, pages={1–12} }
 @article{gonzalez-morales_thomson_yeatts_enomoto_haija_santangelo_petritz_crespo_schal_baynes_2023, title={Pharmacokinetics of fluralaner as a systemic drug to control infestations of the common bed bug, <i>Cimex lectularius</i>, in poultry facilities}, volume={16}, ISSN={["1756-3305"]}, url={https://doi.org/10.1186/s13071-023-05962-3}, DOI={10.1186/s13071-023-05962-3}, abstractNote={Abstract
                Background
                Bed bug infestations are re-emerging in the poultry industry throughout the USA. Although the impacts of bed bugs on birds’ health and welfare are poorly understood, adverse outcomes are expected, including stress, anemia, infections and lower production rates. Worker welfare is also an important consideration in commercial poultry farms. A limited number of insecticides are available for use in the complex spatial environment of commercial farms. Systemic drugs have the potential to overcome the limitations of existing pest management tactics. A recent study showed that fluralaner administered to chickens caused high levels of mortality in bed bugs.
              
                Methods
                To further understand the efficacy of this approach, we evaluated the pharmacokinetics of an oral solid formulation of fluralaner in 11 chickens and quantified its plasma concentration in chickens using UPLC/MS. We administered fluralaner to chickens with two doses of Bravecto® (each 0.5 mg/kg body mass) via gavage 1 week apart and evaluated its efficacy on bed bugs that fed on medicated chickens for up to 28 days post-treatment.
              
                Results
                Bed bugs that fed on fluralaner-treated chickens experienced > 50% mortality within 30 min of the administration of Bravecto and 100% mortality 2 days post-treatment. Mortality slowly declined to 66.6% by day 28. Fluralaner was quantifiable in the hens’ plasma for at least 28 days post-treatment. The treatment resulted in maximal plasma concentrations (Cmax) of 106.4 ng/ml around day 9.0 (Tmax), substantially higher than the LC90, the concentration needed to kill 90% of the bed bugs.
              
                Conclusions
                Fluralaner appears to be a promising candidate for bed bug control in poultry farms, with a treatment effect lasting at least 28 days.
              
                Graphical Abstract
                
              }, number={1}, journal={PARASITES & VECTORS}, author={Gonzalez-Morales, Maria A. and Thomson, Andrea E. and Yeatts, James and Enomoto, Hiroko and Haija, Ahmed and Santangelo, Richard G. and Petritz, Olivia A. and Crespo, Rocio and Schal, Coby and Baynes, Ronald}, year={2023}, month={Sep} }
 @article{elliot_enomoto_petritz_crespo_yeatts_fricke_singleton_thomson_baynes_2024, title={Pharmacokinetics of intravenously and trans-dermally administered fluralaner in healthy laying shaver hens: fluralaner in chickens}, volume={103}, ISSN={["1525-3171"]}, DOI={10.1016/j.psj.2023.103362}, abstractNote={Ectoparasite infestations negatively affect both backyard and commercial chicken flocks in the US. Fluralaner is an isoxazoline shown to be efficacious in treating mite and bed bug infestations in poultry. Fluralaner is approved to treat fleas and ticks in dogs and cats in the US and to treat mite infestations of chickens in Europe and Australia; however, the use of fluralaner in poultry is not yet approved in the US. This study aimed to investigate the plasma fluralaner pharmacokinetic profile of intravenous and transdermal routes and apparent bioavailability of fluralaner administered trans-dermally in healthy shaver hens. A total of 12 individually housed healthy shaver hens received a single dose of either intravenous technical grade fluralaner at 0.5 mg/kg, or transdermal fluralaner (Bravecto® (fluralaner transdermal solution) for dogs, 280 mg/mL, Merck Animal Health) at mean 58.7 mg/kg. Plasma from each hen was collected from the jugular, ulnar or medial metatarsal vein at multiple intervals. Fluralaner concentrations in plasma were determined using Ultra Performance Liquid Chromatography with Mass Spectrometry (UPLC/MS). Non-compartmental analysis revealed that the geometric mean elimination half-life for intravenous and transdermal routes were 80.5 and 179.6 hours, respectively. The geometric mean apparent bioavailability of transdermal routes was estimated as 3.4 %. Prolonged fluralaner concentration in plasma above minimum inhibitory concentration of bed bugs following the single dose was observed in healthy shaver hens for both routes. It is important to understand the pharmacokinetic profile could be useful in determining the appropriate treatment strategy.}, number={3}, journal={POULTRY SCIENCE}, author={Elliot, Baxter A. and Enomoto, Hiroko and Petritz, Olivia and Crespo, Rocio and Yeatts, James and Fricke, Isabel and Singleton, Abby and Thomson, Andrea and Baynes, Ronald E.}, year={2024}, month={Mar} }
 @article{papich_madsen_messenger_enomoto_2022, title={Ceftazidime pharmacokinetics in dogs after intravenous injection and delivered with the RxActuator Mini-Infuser infusion pump}, volume={5}, ISSN={["1476-4431"]}, url={https://doi.org/10.1111/vec.13205}, DOI={10.1111/vec.13205}, abstractNote={AbstractObjectiveTo test the feasibility of an SC mini‐infusion pump to deliver ceftazidime in dogs and produce plasma concentrations sufficient to reach a therapeutic target for 48 hours.SettingUniversity research laboratory.AnimalsSix healthy Beagle dogs.InterventionsCeftazidime was administered by 2 routes to 6 healthy Beagle dogs. The first route was an IV bolus injection into a cephalic vein at a dose of 25 mg/kg. Blood samples were collected for 8 hours following injection. The second route was a SC infusion for 48 hours using the RxActuator Mini‐Infuser wearable SC constant rate infusion pump. Blood samples were collected for 58 hours following application of the pump. All plasma samples were analyzed by high‐pressure liquid chromatography and subject to pharmacokinetic analysis.Main ResultsAfter the IV bolus injection, there was rapid distribution and elimination. The elimination half‐life was 0.95 hours, and the clearance was rapid at 0.176 ml/h/kg. After the 48‐hour SC infusion, the half‐life was slightly shorter, and the clearance was higher. The percent bioavailability from the SC infusion was approximately 72%. The SC infusion maintained plasma concentration near our target of 8 μg/ml for most of the dose interval but slightly lower after 24 hours. The concentrations below the target were attributed to slight drug loss, less than 100% bioavailability, and faster clearance from SC administration.ConclusionsThis study demonstrated the successful application of the RxActuator Mini‐Infuser wearable SC constant rate infusion pump for delivering an antimicrobial needed for serious, and sometimes resistant, infections in dogs.}, journal={JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE}, author={Papich, Mark G. and Madsen, Melanie and Messenger, Kristen and Enomoto, Hiroko}, year={2022}, month={May} }
 @article{werners_karasek_butler_yeatts_enomoto_baynes_2022, title={Control of ticks on horses using abamectin-impregnated ear tags. A pharmacokinetic and pharmacodynamic study}, volume={6}, ISSN={["1365-2885"]}, url={https://doi.org/10.1111/jvp.13084}, DOI={10.1111/jvp.13084}, abstractNote={AbstractSeveral different tick species are known to infest horses. Aside from causing serious health and welfare issues, including anaemia, ill thrift, and immunosuppression, ticks can transmit a variety of important, sometimes zoonotic, pathogens. The successful prevention and treatment of tick infestations have been described, but the information is scarce and, in many instances, anecdotal. Here we describe a practical and affordable prevention of tick infestation by using abamectin‐impregnated cattle ear tags affixed to a safety collar. We have assessed the radial distribution of abamectin by analyzing hair samples, as well as its efficacy against tick infestations. The study results show that abamectin distributes across horse skin from the site of application and its associated effectiveness in reducing the tick burden.}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, publisher={Wiley}, author={Werners, Arno and Karasek, Inga and Butler, Catherine and Yeatts, James and Enomoto, Hiroko and Baynes, Ronald}, year={2022}, month={Jun} }
 @article{enomoto_love_madsen_wallace_messenger_2022, title={Pharmacokinetics of intravenous, oral transmucosal, and intranasal buprenorphine in healthy male dogs}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.13056}, abstractNote={AbstractEffective management of pain in animals is of critical importance but options are limited for treating acute pain in dogs on an outpatient basis. The objective of this study was to compare the plasma concentrations and pharmacokinetics of a concentrated solution of buprenorphine, 1.8 mg/ml (Simbadol™) administered intravenously, intranasally, and via the oral transmucosal (OTM) route in healthy male dogs. Five healthy castrated adult male Beagle‐cross dogs were included in this randomized blocked crossover study. The dogs received 0.03 mg/kg body weight buprenorphine intravenously, intranasally, or via the OTM route, with a minimum 72‐h washout period between treatments. Blood samples were collected at multiple intervals up to 24 h post administration and buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. Non‐compartmental pharmacokinetic analysis revealed that the area under the curve of intravenous, intranasal, and OTM routes were 28.0 (15.1–41.3) h × ng/ml, 16.1 (3.4–28.7) h × ng/ml and 10.8 (8.8–11.8) h × ng/ml, respectively. The bioavailability of intranasal and OTM routes were 57.5 (22.7–93.7)% and 41.1 (25.5–69.4)%, respectively. Intranasal and OTM routes of administration of concentrated buprenorphine in dogs may allow for the provision of analgesic care at home.}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Enomoto, Hiroko and Love, Lydia and Madsen, Melanie and Wallace, Amber and Messenger, Kristen M.}, year={2022}, month={Apr} }
 @article{southern_long_barnes_enomoto_messenger_2022, title={Preliminary evaluation of the effects of grapiprant compared with carprofen on acute pain and inflammation following ovariohysterectomy in dogs}, volume={83}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.21.10.0162}, abstractNote={Abstract

OBJECTIVE
To compare the analgesic efficacy of grapiprant to carprofen for the treatment of postoperative pain and inflammation in dogs following ovariohysterectomy.


ANIMALS
12 purpose-bred adult sexually intact female Beagles.


PROCEDURES
Dogs were randomly assigned to 1 of 2 treatment groups: grapiprant (2 mg/kg, PO; n = 6) or carprofen (4.4 mg/kg, PO; n = 6), 1.5 hours prior to ovariohysterectomy (OVH) and every 24 hours afterward for 3 total doses. An ultrafiltration probe was placed within the OVH incision to collect interstitial fluid (ISF). Pain and inflammation were assessed by masked investigators via mechanical nociceptive threshold testing and the short form of the Glasgow Composite Pain Scale before drug administration and at multiple time points for 72 hours following dosing and surgery. ISF samples were collected at the same time points to assess prostaglandin E2 concentrations at the site of inflammation.


RESULTS
In both groups, pain scale scores were highest in the immediate postoperative period and decreased over time. In both treatment groups, there were significant (P = 0.003) differences in mechanical nociceptive threshold results over time when compared with baseline, but there was no difference between groups. Prostaglandin E2 concentrations in ISF were higher in dogs receiving grapiprant compared with carprofen (P < 0.001). One dog in the carprofen group required rescue analgesia.


CLINICAL RELEVANCE
Results of this preliminary study suggested both carprofen and grapiprant may be effective for postoperative pain following OVH in dogs; however, additional studies are warranted to determine grapiprant’s effectiveness in a larger and more diverse population of dogs.
}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Southern, Brittany L. and Long, Sarah M. and Barnes, Danielle N. and Enomoto, Hiroko and Messenger, Kristen M.}, year={2022}, month={Jul} }
 @article{madsen_enomoto_messenger_papich_2022, title={Effects of housing environment on oral absorption of acetaminophen in healthy Beagles}, volume={83}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.21.06.0075}, abstractNote={Abstract

OBJECTIVE
To evaluate the effects of housing environment on oral absorption of acetaminophen in dogs.


ANIMALS
6 healthy Beagles.


PROCEDURES
Acetaminophen (325 mg, PO; mean dose, 31.1 mg/kg) was administered in a crossover study design with dogs housed in their normal environment or in a cage in an unfamiliar environment. There was a 7-day washout period between phases. Blood samples were collected for 24 hours following acetaminophen administration, and plasma acetaminophen concentrations were determined with high-pressure liquid chromatography.


RESULTS
A 2-compartment model with lag time was the best fit for both phases of the study. None of the primary or secondary pharmacokinetic parameters were significantly different between the 2 housing environments.


CLINICAL RELEVANCE
Findings suggested that in dogs, housing environment (normal environment vs a cage in an unfamiliar environment) did not significantly affect oral absorption and, by extension, gastric emptying of acetaminophen.
}, number={1}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Madsen, Melanie and Enomoto, Hiroko and Messenger, Kristen and Papich, Mark G.}, year={2022}, month={Jan}, pages={80–85} }
 @article{enomoto_petritz_thomson_flammer_ferdous_meyer_tell_baynes_2021, title={Egg residue and depletion in Rhode Island Red hens (Gallus gallus domesticus) following multiple oral doses of trimethoprim-sulfamethoxazole}, volume={123}, ISSN={["1096-0295"]}, url={https://doi.org/10.1016/j.yrtph.2021.104941}, DOI={10.1016/j.yrtph.2021.104941}, abstractNote={Sulfamethoxazole-Trimethoprim residues in eggs can cause risks to human health. The most common cause of residues in eggs results from failure to meet an appropriate withdrawal interval. The aim of this study was to determine the quantity and duration of sulfamethoxazole-trimethoprim residues in eggs and evaluate the drug elimination parameters in egg components and whole egg to better estimate the withdrawal interval of sulfamethoxazole and trimethoprim following oral administration for 7 days at a purposed dosage regimen (time average 46 mg kg-1 day-1 for sulfamethoxazole, time average 25 mg kg-1 day-1 for trimethoprim). Residues of sulfamethoxazole and trimethoprim in albumen and yolk were analyzed by ultra-performance liquid chromatography mass spectrometry. A greater percentage of sulfamethoxazole was distributed into the albumen (91.53-96.74%) and a greater percentage of trimethoprim was distributed into yolk (63.92-77.36%) during treatment. The residues levels in whole egg declined below or reached the limit of quantification until 13 days for SMZ and TMP respectively. The withdrawal interval for SMZ and TMP were 43 days and 17 days respectively using the FDA tolerance method.}, journal={REGULATORY TOXICOLOGY AND PHARMACOLOGY}, publisher={Elsevier BV}, author={Enomoto, Hiroko and Petritz, Olivia A. and Thomson, Andrea E. and Flammer, Keven and Ferdous, Farha and Meyer, Emma and Tell, Lisa A. and Baynes, Ronald E.}, year={2021}, month={Jul} }
 @article{enomoto_yeatts_carbajal_krishnan_madan_laumas_blikslager_messenger_2021, title={In vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model}, volume={16}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0249179}, abstractNote={There is no FDA approved therapy for the treatment of celiac disease (CeD), aside from avoidance of dietary gluten. Larazotide acetate (LA) is a first in class oral peptide developed as a tight junction regulator, which is a lead candidate for management of CeD. A delayed release formulation was tested in vitro and predicted release in the mid duodenum and jejunum, the target site of CeD. The aim of this study was to follow the concentration versus time profile of orally administered LA in the small intestine using a porcine model. A sensitive liquid chromatography/tandem mass spectrometry method was developed to quantify LA concentrations in porcine intestinal fluid samples. Oral dosing of LA (1 mg total) in overnight fasted pigs resulted in time dependent appearance of LA in the distal duodenum and proximal jejunum. Peak LA concentrations (0.32–1.76 μM) occurred at 1 hour in the duodenum and in proximal jejunum following oral dosing, with the continued presence of LA (0.02–0.47 μM) in the distal duodenum and in proximal jejunum (0.00–0.43 μM) from 2 to 4 hours following oral dosing. The data shows that LA is available in detectable concentrations at the site of CeD.}, number={4}, journal={PLOS ONE}, author={Enomoto, Hiroko and Yeatts, James and Carbajal, Liliana and Krishnan, B. Radha and Madan, Jay P. and Laumas, Sandeep and Blikslager, Anthony T. and Messenger, Kristen M.}, year={2021}, month={Apr} }