@article{mzyk_halleran_sylvester_giles_jacob_baynes_foster_2024, title={Continuous sampling of healthy and mastitic quarters of lactating cattle by ultrafiltration after intramammary ceftiofur hydrochloride administration}, volume={8}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.17155}, DOI={10.1111/jvim.17155}, abstractNote={Abstract Background Pharmacological activity of intramammary drugs depends on adequate drug concentrations within the cistern, but sampling is often limited. Insight into the active drug concentration within the mammary cistern may assist in determining effective and appropriate therapeutic decisions for cows being treated for mastitis. Objective Evaluate the disposition of ceftiofur hydrochloride administered intramammary in diseased and nondiseased quarters. Whole milk and ultrafiltrate sampling techniques were compared. Animals Ten mature, late lactation Holstein (n = 9) and Jersey (n = 1) dairy cows (422‐670 kg) with naturally occurring clinical mastitis, producing between 1.4 and 15.9 kg/day of milk. Methods Ultrafiltration probes were placed in both mastitic and healthy quarters. Each quarter was treated with 2 doses of 125 mg ceftiofur hydrochloride suspension, and whole milk and milk ultrafiltrate samples were collected. Ceftiofur concentrations in composite whole milk and milk ultrafiltrate were analyzed. Results The maximum concentration of ceftiofur was higher in ultrafiltrate samples, but no differences were identified in healthy or mastitic quarters. The use of ultrafiltration probes provides a novel technique for free drug concentrations within the mastitic and healthy bovine mammary gland. Conclusions and Clinical Importance Significant inter‐ and intracow variability and lower daily milk weights may overestimate ceftiofur concentrations available within the cistern. The pharmacokinetic (PK) parameters reported in milk ultrafiltrate will help establish a link between the PK and the corresponding drug effect, potentially providing a meaningful rationale for the selection of a safe and effective dose in cows with mastitis.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Mzyk, Danielle A. and Halleran, Jennifer L. and Sylvester, Hannah J. and Giles, Claire B. and Jacob, Megan E. and Baynes, Ronald E. and Foster, Derek M.}, year={2024}, month={Aug} }
 @article{giles_ferdous_halleran_yeatts_baynes_mzyk_2024, title={Flunixin meglumine tissue residues after intravenous administration in goats}, volume={10}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2023.1341779}, abstractNote={BackgroundFlunixin is commonly used in goats in an extra-label manner, indicating a significant need to determine withdrawal intervals for edible tissues.ObjectiveThe objectives of the present study were to investigate the depletion of flunixin meglumine in various goat tissues, including the liver, kidney, fat, and muscle.MethodsTwenty Boer goats were enrolled and administered an intravenous dose (2.2 mg/kg) of flunixin meglumine. Five animals were randomly euthanized at 24, 48, 72, or 96 h following dosing. All samples were analyzed via ultra-performance liquid chromatography coupled with mass spectrometry.ResultsThe concentration of flunixin in all tissues declined rapidly, with the highest mean concentrations quantified in the kidney (0.137 ± 0.062 μg/g) and liver (0.077 ± 0.029 μg/g) tissues at 24 h.ConclusionSince any detection of flunixin residues at slaughter found in goat tissues is considered a violative residue, a conservative withdrawal interval of 17 days was calculated to ensure levels of flunixin fell below the regulatory limits of detection in liver, kidney, and muscle tissues.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Giles, Claire B. and Ferdous, Farha and Halleran, Jennifer L. and Yeatts, Jim L. and Baynes, Ronald E. and Mzyk, Danielle A.}, year={2024}, month={Jan} }
 @article{mzyk_giles_baynes_smith_2023, title={Milk residues following multiple doses of meloxicam and gabapentin in lactating dairy cattle}, volume={261}, ISSN={["1943-569X"]}, url={http://dx.doi.org/10.2460/javma.23.06.0329}, DOI={10.2460/javma.23.06.0329}, abstractNote={Abstract

OBJECTIVE
To determine the influence of stage of lactation on the pharmacokinetics in milk when multiple doses of meloxicam were administered alone or in combination with gabapentin to postpartum (PP) and mid-lactation (ML) cows.


ANIMALS
8 postpartum and 8 mid-lactation dairy cows.


METHODS
Cows were randomly divided into 2 groups (n = 8) which included 4 PP cows and 4 ML cows. Group I received only 6 oral daily doses of meloxicam (1.0 mg/kg for 6 doses). Group II received 6 oral daily doses of co-administered meloxicam (1.0 mg/kg) and gabapentin (20 mg/kg) for 6 doses. Meloxicam and gabapentin were quantified in plasma and milk samples by ultra–high-performance liquid chromatography–tandem mass spectrometry, and the pharmacokinetic analysis of milk and plasma was performed using a non-compartmental approach.


RESULTS
Regardless of lactation status, dairy cattle administered multiple doses of meloxicam and/or gabapentin showed low drug residue concentrations and little accumulation in milk. The terminal plasma half-life of meloxicam was significantly increased (P < .02) in PP cows (12.9 hr) compared to ML cows (9.4 hr). The apparent terminal half-life in milk for meloxicam and gabapentin was not affected by stage of lactation. Co-administration of gabapentin did not alter plasma or milk concentrations of meloxicam.


CLINICAL RELEVANCE
The results of this study suggest that milk from cows treated with multiple doses of meloxicam alone or in combination with gabapentin will have low drug concentrations and falls below our reported limit of detection for meloxicam or gabapentin 120 and 60 hours respectively, following the final dose regardless of their stage of lactation.
}, number={12}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, publisher={American Veterinary Medical Association (AVMA)}, author={Mzyk, Danielle A. and Giles, Claire B. and Baynes, Ronald E. and Smith, Geof W.}, year={2023}, month={Dec}, pages={1873–1879} }
 @article{smith_bublitz_nixon_yeatts_ball_baynes_2021, title={EVALUATION OF THE PHARMACOKINETIC BEHAVIOR OF TULATHROMYCIN (DRAXXIN) IN FLORIDA MANATEES (TRICHECHUS MANATUS LATIROSTRIS) UNDERGOING MEDICAL REHABILITATION}, volume={52}, ISSN={["1937-2825"]}, url={http://dx.doi.org/10.1638/2021-0025}, DOI={10.1638/2021-0025}, abstractNote={Abstract: Florida manatees (Trichechus manatus latirostris) frequently present to rehabilitation care facilities for various conditions, including boat strike trauma, cold stress syndrome, and brevetoxicosis. Throughout the course of treatment, antimicrobial use to treat respiratory disease is frequently warranted. To date, clinicians have extrapolated dosages based on established information available in bovine and equine medicine. The routes of administration, efficacy, and treatment intervals are considerations in dealing with critical wild animals. The use of tulathromycin, a triamilide antibiotic, has been studied in multiple domestic species of economic importance, including cattle, small ruminants, and swine, and has revealed efficacy against respiratory diseases. Given this information, this antibiotic has also been used in manatees with positive clinical outcomes. This study employed sparse sampling and evaluated banked plasma samples at various time intervals post–tulathromycin administration obtained during the clinical treatment course of nine animals during their rehabilitation. Preliminary pharmacokinetic analysis following administration of a single dose estimated a half-life of 33.75 h and volume of distribution per fraction absorbed (Vz/F = 4.29 L/kg). The pharmacokinetic behavior of tulathromycin in Florida manatees can be used to optimize dosage regimens in this species.}, number={3}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, publisher={American Association of Zoo Veterinarians}, author={Smith, Lauren N. and Bublitz, Claire and Nixon, Emma and Yeatts, James and Ball, Ray L. and Baynes, Ronald E.}, year={2021}, month={Sep}, pages={880–885} }
 @article{bublitz_mzyk_mays_fajt_hairgrove_baynes_2019, title={Comparative plasma and urine concentrations of flunixin and meloxicam in goats}, volume={174}, ISBN={1879-0941}, DOI={10.1016/j.smallrumres.2019.01.013}, abstractNote={The objective of this study was to compare plasma and urine concentrations of flunixin and meloxicam, in order to determine withdrawal intervals for animals at livestock shows where urine is routinely tested. Eleven goats were housed in individual metabolism cages to facilitate complete urine collection. All animals were randomly divided into one of two treatment groups and received either a single dose of 2.2 mg/kg flunixin in the muscle (n = 5) or 0.5 mg/kg meloxicam by mouth (n = 6). Flunixin meglumine was given via an intramuscular injection to evaluate the effect of extra label administration on the disposition of flunixin in goats. The information from this study represents a potential worst-case scenario for urine depletion and helps determine the withdrawal intervals needed for flunixin meglumine in show goats when administered in this extra label manner. Plasma and urine samples were collected over 360 h and analyzed by tandem mass spectrometry (UPLC-MS-MS). Goats were euthanized at the end of the study, and liver samples were collected at necropsy 15 days post dose in order to quantify any potential residues. Drug levels in urine reached peak concentrations between 8 and 16 h after dosing for both drugs. Flunixin urine concentrations were higher than maximum levels determined in plasma. Urine concentrations for both flunixin and meloxicam fell below the limit of detection (LOD) of 1.0 ng/mL by 240 h in all goats. Calculated harmonic mean apparent elimination half-life in plasma based on non-compartmental analysis was 5.4 ± 0.001 h and 10.3 ± 0.001 h for flunixin and meloxicam respectively. Five of six liver samples for goats administered meloxicam fell below the limit of quantification (LOQ) of 5.0 ng/mL by 15 days. Four out of five liver samples for goats administered flunixin fell below the LOQ (5.0 ng/mL) by 15 days. Flunixin and meloxicam administered to healthy goats exhibited longer elimination from urine than plasma, but followed a similar and linear depletion profile. Urine concentrations did not correlate with liver residues. This study provides useful information that can assist livestock show authorities and veterinarians determine an appropriate withdrawal interval for show animals whose urine may be tested prior to competition.}, journal={SMALL RUMINANT RESEARCH}, author={Bublitz, Claire M. and Mzyk, Danielle A. and Mays, Travis and Fajt, Virginia R. and Hairgrove, Thomas and Baynes, Ronald E.}, year={2019}, month={May}, pages={40–46} }
 @article{mzyk_bublitz_martinez_davis_baynes_smith_2019, title={Impact of bovine respiratory disease on the pharmacokinetics of danofloxacin and tulathromycin in different ages of calves}, volume={14}, ISSN={["1932-6203"]}, url={http://dx.doi.org/10.1371/journal.pone.0218864}, DOI={10.1371/journal.pone.0218864}, abstractNote={Pneumonia is one of the most economically important respiratory diseases of calves and knowledge of the impact of clinical disease on pharmacokinetics (PK) in young calves is limited. This study was undertaken to investigate the efficacy and PK of two antibiotics, tulathromycin and danofloxacin, in two age groups of calves experimentally infected with Pasteurella multocida. Both danofloxacin, a fluoroquinolone antibiotic, and tulathromycin, a macrolide antibiotic is approved for the treatment of bovine respiratory disease (BRD). To evaluate potential influences of age and disease on drug distribution and elimination in calves, plasma, interstitial fluid (ISF), and pulmonary epithelial lining fluid (PELF) were analyzed for drug concentrations. Concentrations for both drugs in the PELF were estimated by a urea dilution assay of the collected bronchoalveolar lavage fluids. Age was determined to be a significant covariate for calves administered danofloxacin and tulathromycin for plasma PK parameters. For calves administered danofloxacin, the area under the curve (AUC) in the plasma was lower in 6-month old calves (18.9 ± 12.6 hr* μg/mL) vs. 3-week old calves (32.0 ± 8.2 hr* μg/mL). Clearance (CL/F) of danofloxacin was higher in 6-month old calves. In contrast, tulathromycin plasma concentrations were higher in 6 month old calves and CL/F was higher in 3-week old calves. Age did not significantly influence the ISF concentrations of danofloxacin or tulathromycin in calves with respiratory disease, unlike previous studies which reported higher ISF concentrations of danofloxacin and tulathromycin in 6-month old calves when compared to younger calves. PELF concentrations were higher than plasma and ISF for both danofloxacin and tulathromycin, but did not differ between age groups. Potential reasons for age-related differences on plasma concentration–time profiles and the impact of disease on the partitioning of the drug from the blood to the lungs and ISF as a function of age are explored.}, number={6}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Mzyk, Danielle A. and Bublitz, Claire M. and Martinez, Marilyn N. and Davis, Jennifer L. and Baynes, Ronald E. and Smith, Geof W.}, editor={Gladue, DouglasEditor}, year={2019}, month={Jun} }
 @article{mzyk_bublitz_hobgood_martinez_davis_smith_baynes_2018, title={Effect of age on plasma protein binding of several veterinary drugs in dairy Check for calves 2}, volume={121}, ISSN={["1532-2661"]}, DOI={10.1016/j.rvsc.2018.09.004}, abstractNote={The intent of this study was to determine what influence, if any, increasing age has on the binding of drugs to plasma proteins in cattle. Plasma from three different cohorts of calves were used. The first group (n = 20) had plasma samples taken at 1, 7 and 21 days of age. These were compared to results from a second group of calves at 8 weeks and third group sampled at 6 months of age. The plasma protein binding of danofloxacin, florfenicol, flunixin meglumine and tulathromycin was determined in vitro via microcentrifugation using three different drug concentrations spiked into the individual plasma samples derived from each calf. Albumin concentrations were lowest at 1 day of age as compared to plasma samples taken from 2 month old and 6 month old calves. There were significant decreases in alpha1-acid glycoprotein in calves until 21 days of age. However, statistically significant age-effects on plasma protein binding were not observed for any of the drugs evaluated in this study. Findings from these calves suggest that age is not an important factor in the binding of these drugs to plasma proteins.}, journal={RESEARCH IN VETERINARY SCIENCE}, author={Mzyk, Danielle A. and Bublitz, Claire M. and Hobgood, Ginger D. and Martinez, Marilyn N. and Davis, Jennifer L. and Smith, Geof W. and Baynes, Ronald E.}, year={2018}, month={Dec}, pages={59–64} }
 @article{mzyk_bublitz_sylvester_mullen_hobgood_baynes_foster_2018, title={Short communication: Use of an ultrafiltration device in gland cistern for continuous sampling of healthy and mastitic quarters of lactating cattle for pharmacokinetic modeling.}, volume={101}, url={https://doi.org/10.3168/jds.2018-14849}, DOI={10.3168/jds.2018-14849}, abstractNote={Pharmacokinetic studies of the drugs in the milk are often limited due to infrequent sampling associated with milking. Alternatively, frequent sample collection with repeated milking may increase drug elimination. The objective of this study was to determine the feasibility of continuously sampling the udder using ultrafiltration. An ultrafiltration probe was placed into the gland cisterns through mammary parenchyma of normal and mastitic quarters of 6 mature mid-lactation Jersey cows with naturally occurring subclinical mastitis. An ultrafiltration probe was secured to the caudal or lateral aspect of the udder depending on the quarter being sampled. The timed interval samples were collected at 0, 2, 4, 6, 8, 12, 18, 24, 28, 32, 36, 48, 60, 72, 84, and 96 h after drug administration. Plasma samples were collected at the same time points. Each cow received 2.2 mg/kg of flunixin intravenously before milking at time 0. All cows were routinely milked by machine every 12 h. Flunixin concentrations in plasma, whole milk, and milk ultrafiltrates were analyzed by use of ultra-high-performance liquid chromatography with mass spectrometric detection. We found no significant effects on the appearance of the milk or the ability to milk the cows after implantation of the ultrafiltration probes. The concentration of flunixin collected from the ultrafiltration probes in the mastitic quarters tended to be greater than that of the healthy quarters. We concluded that collection of ultrafiltration samples from the mammary gland of cows provides a viable means to continuously assess drug concentrations in the milk while continuing to milk the cow normally. This study demonstrates the utility of continuous sampling of milk via ultrafiltration for future pharmacokinetic studies in cattle.}, number={11}, journal={Journal of dairy science}, author={Mzyk, D. A. and Bublitz, C. M. and Sylvester, H. and Mullen, K. A. E. and Hobgood, G. D. and Baynes, R. E. and Foster, Derek}, year={2018}, month={Sep}, pages={10414–10420} }
 @article{bublitz_mzyk_mays_fajt_hairgrove_baynes, title={Comparative urine residues of flunixin and meloxicam in show goats}, volume={41}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Bublitz, C. M. and Mzyk, D. A. and Mays, T. and Fajt, V. R. and Hairgrove, T. and Baynes, R. E.}, pages={24–24} }
 @article{mzyk_bublitz_martinez_davis_baynes_smith, title={Impact of bovine respiratory disease on the pharmacokinetics of danofloxacin and tulathromycin in different ages of calves}, volume={41}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Mzyk, D. A. and Bublitz, C. M. and Martinez, M. N. and Davis, J. L. and Baynes, R. E. and Smith, G. W.}, pages={33–33} }