@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.}, 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{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 United States. 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 United States and to treat mite infestations of chickens in Europe and Australia; however, the use of fluralaner in poultry is not yet approved in the United States. 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). Noncompartmental analysis revealed that the geometric mean elimination half-life for intravenous and transdermal routes were 80.5 and 179.6 h, 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{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, Cimex lectularius, 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}, 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{werners_karasek_butler_yeatts_enomoto_baynes_2022, title={Control of ticks on horses using abamectin-impregnated ear tags. A pharmacokinetic and pharmacodynamic study}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.13084}, abstractNote={Abstract}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Werners, Arno and Karasek, Inga and Butler, Catherine and Yeatts, James and Enomoto, Hiroko and Baynes, Ronald}, year={2022}, month={Jun} } @article{meira_wiloch_nixon_yeatts_sheela_smith_baynes_2022, title={The pharmacokinetics of transdermal flunixin in lactating dairy goats}, volume={105}, ISSN={["1525-3198"]}, url={https://doi.org/10.3168/jds.2021-20460}, DOI={10.3168/jds.2021-20460}, abstractNote={Flunixin is a nonsteroidal anti-inflammatory drug approved for use in cattle to manage pyrexia associated with bovine respiratory disease, mastitis, and endotoxemia. In the United States, no nonsteroidal anti-inflammatory drugs are approved for use in goats, but analgesics are needed for management of painful conditions to improve animal welfare. The objective of this study was to evaluate the pharmacokinetics of transdermal flunixin in dairy goats to determine a milk withdrawal interval (WDI) to avoid violative residue contamination in the food supply. Six adult lactating dairy goats received 3.3 mg/kg of transdermal flunixin before milk, interstitial fluid (ISF), and blood samples were collected at various time points for 360 h. The samples were analyzed using tandem mass spectrometry to detect flunixin as well as the flunixin marker metabolite, 5-hydroxyflunixin followed by a pharmacokinetic WDI calculation using the US Food and Drug Administration tolerance limit method to propose safe residue levels in goat milk. The mean flunixin apparent plasma half-life was 21.63 h. The apparent milk half-life for 5-hydroxyflunixin was 17.52 h. Our findings provide a milk WDI of 60 h using the US Food and Drug Administration tolerance of 0.002 µg/mL (established for bovine milk) and a more conservative WDI of 96 h using a limit of quantification of 0.001 µg/mL following the extralabel use of transdermal flunixin in dairy goats.}, number={1}, journal={JOURNAL OF DAIRY SCIENCE}, publisher={American Dairy Science Association}, author={Meira, Enoch B. de S., Jr Jr and Wiloch, Emily E. and Nixon, Emma and Yeatts, James L. and Sheela, Farha Ferdous and Smith, Geof W. and Baynes, Ronald E.}, year={2022}, month={Jan}, pages={549–559} } @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{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} } @article{nixon_mays_routh_yeatts_fajt_hairgrove_baynes_2020, title={Plasma, urine and tissue concentrations of Flunixin and Meloxicam in Pigs}, volume={16}, ISSN={["1746-6148"]}, DOI={10.1186/s12917-020-02556-4}, abstractNote={Abstract}, number={1}, journal={BMC VETERINARY RESEARCH}, author={Nixon, Emma and Mays, Travis P. and Routh, Patricia A. and Yeatts, James L. and Fajt, Virginia R. and Hairgrove, Thomas and Baynes, Ronald E.}, year={2020}, month={Sep} } @article{westermeyer_salmon_baynes_yeatts_khattab_oh_mowat_2019, title={Safety and efficacy of topically applied 0.5% and 1% pirfenidone in a canine model of subconjunctival fibrosis}, volume={22}, ISSN={["1463-5224"]}, url={https://doi.org/10.1111/vop.12619}, DOI={10.1111/vop.12619}, abstractNote={Abstract}, number={4}, journal={VETERINARY OPHTHALMOLOGY}, author={Westermeyer, Hans D. and Salmon, Beth and Baynes, Ronald and Yeatts, James and Khattab, Ahlam and Oh, Annie and Mowat, Freya}, year={2019}, month={Jul}, pages={502–509} } @article{howard_ashwell_baynes_brooks_yeatts_maltecca_2018, title={Genetic Parameter Estimates for Metabolizing Two Common Pharmaceuticals in Swine}, volume={9}, ISSN={1664-8021}, url={http://dx.doi.org/10.3389/fgene.2018.00040}, DOI={10.3389/fgene.2018.00040}, abstractNote={In livestock, the regulation of drugs used to treat livestock has received increased attention and it is currently unknown how much of the phenotypic variation in drug metabolism is due to the genetics of an animal. Therefore, the objective of the study was to determine the amount of phenotypic variation in fenbendazole and flunixin meglumine drug metabolism due to genetics. The population consisted of crossbred female and castrated male nursery pigs (n = 198) that were sired by boars represented by four breeds. The animals were spread across nine batches. Drugs were administered intravenously and blood collected a minimum of 10 times over a 48 h period. Genetic parameters for the parent drug and metabolite concentration within each drug were estimated based on pharmacokinetics (PK) parameters or concentrations across time utilizing a random regression model. The PK parameters were estimated using a non-compartmental analysis. The PK model included fixed effects of sex and breed of sire along with random sire and batch effects. The random regression model utilized Legendre polynomials and included a fixed population concentration curve, sex, and breed of sire effects along with a random sire deviation from the population curve and batch effect. The sire effect included the intercept for all models except for the fenbendazole metabolite (i.e., intercept and slope). The mean heritability across PK parameters for the fenbendazole and flunixin meglumine parent drug (metabolite) was 0.15 (0.18) and 0.31 (0.40), respectively. For the parent drug (metabolite), the mean heritability across time was 0.27 (0.60) and 0.14 (0.44) for fenbendazole and flunixin meglumine, respectively. The errors surrounding the heritability estimates for the random regression model were smaller compared to estimates obtained from PK parameters. Across both the PK and plasma drug concentration across model, a moderate heritability was estimated. The model that utilized the plasma drug concentration across time resulted in estimates with a smaller standard error compared to models that utilized PK parameters. The current study found a low to moderate proportion of the phenotypic variation in metabolizing fenbendazole and flunixin meglumine that was explained by genetics in the current study.}, number={FEB}, journal={Frontiers in Genetics}, publisher={Frontiers Media SA}, author={Howard, Jeremy T. and Ashwell, Melissa S. and Baynes, Ronald E. and Brooks, James D. and Yeatts, James L. and Maltecca, Christian}, year={2018}, month={Feb} } @article{howard_ashwell_baynes_brooks_yeatts_maltecca_2017, title={Gene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver}, volume={7}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/s41598-017-01526-5}, DOI={10.1038/s41598-017-01526-5}, abstractNote={Abstract}, number={1}, journal={Scientific Reports}, publisher={Springer Nature}, author={Howard, Jeremy T. and Ashwell, Melissa S. and Baynes, Ronald E. and Brooks, James D. and Yeatts, James L. and Maltecca, Christian}, year={2017}, month={May} } @article{mason_mullen_anderson_washburn_yeatts_baynes_2017, title={Pharmacokinetic analysis of thymol, carvacrol and diallyl disulfide after intramammary and topical applications in healthy organic dairy cattle}, volume={34}, ISSN={1944-0049 1944-0057}, url={http://dx.doi.org/10.1080/19440049.2017.1285056}, DOI={10.1080/19440049.2017.1285056}, abstractNote={ABSTRACT Mastitis is among the most costly concerns for dairy producers whether cattle are managed conventionally or organically. Unfortunately, there are no USFDA-approved mastitis treatments that allow dairy cows in the United States to maintain organic dairy status. We investigated the plasma pharmacokinetics of three organic mastitis products currently used by organic producers and organic dairy veterinarians. Those products include intramammary, topical and intravaginal preparations, each dosed at two levels. Additionally, tissue data were collected for kidney, liver and fat in order to estimate a withholding time for each of the products. The lower limit of quantification (LOQ) and lower limit of detection (LOD) were 0.001 and 0.0005 µg ml–1, respectively, in plasma and all tissues except fat for both thymol and carvacrol. Fat had an LOQ of 0.01 µg ml–1 and an LOD of 0.005 µg ml–1 for thymol and carvacrol. Diallyl disulfide had an LOQ of 0.005 µg ml–1 and LOD of 0.001 µg ml–1 in all tissues. For diallyl disulfide (garlic), no levels above 0.001 µg ml–1 were measurable in plasma or tissues. For topical and intramammary products, levels were measurable in the plasma, liver, kidney and fat up to 72 h after the last dose. The plasma half-lives were short for thymol (approximately 1.6 h) and carvacrol (approximately 1.5 h), whereas the estimated half-lives for these substances in tissues ranged from 13.9 to 31.5 h for thymol and from 16.9 to 25 h for carvacrol. The predicted amount of time that the molecules would be found in the body based on the slowest depletion time of liver tissue was 13 days for thymol and 10 days for carvacrol. The apparent half-life of topically applied carvacrol was approximately 4.5 h in plasma, with an estimated withhold time of 10 days. These times were calculated using the USFDA’s tolerance limit method for meat withdrawal times.}, number={5}, journal={Food Additives & Contaminants: Part A}, publisher={Informa UK Limited}, author={Mason, Sharon E. and Mullen, Keena A. E. and Anderson, Kevin L. and Washburn, Steven P. and Yeatts, James L. and Baynes, Ronald E.}, year={2017}, month={Feb}, pages={1–10} } @article{armorini_yeatts_mullen_mason_mehmeti_anderson_washburn_baynes_2016, title={Development of a HS-SPME-GC-MS/MS Method for the Quantitation of Thymol and Carvacrol in Bovine Matrices and To Determine Residue Depletion in Milk and. Tissues}, volume={64}, ISSN={["1520-5118"]}, DOI={10.1021/acs.jafc.6b02899}, abstractNote={Thymol and carvacrol may be present in several phytoceutical products but there are no well-defined methods to measure these compounds in meat and milk from treated animals. U.S. regulatory authorities deem their presence as an adulteration of food. A rapid and sensitive HS-SPME-GC-MS/MS method was developed for the detection of thymol and carvacrol in bovine milk, plasma, liver, kidney, and fat. Inter- and intraday precision values were all less than 15.7 and 20.2% for thymol and carvacrol, respectively. The accuracy was in ranges of 69.9-111.8% for thymol and 74.0-119.2% for carvacrol. With the exception of fat tissue, stability studies showed that both compounds are stable over a 2 month period. A pilot pharmacokinetic study was conducted to evaluate the developed analytical method and to provide initial estimates of thymol and carvacrol depletion in plasma, milk, and several tissues. Treatment of lactating dairy cattle with phytoceutical products containing these substances resulted in low but measurable residue levels at 96 h for liver and 36 h for milk with very short apparent plasma and milk half-lives (<3.0 h).}, number={41}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Armorini, Sara and Yeatts, James E. and Mullen, Keena A. E. and Mason, Sharon E. and Mehmeti, Elmira and Anderson, Kevin L. and Washburn, Steve P. and Baynes, Ronald E.}, year={2016}, month={Oct}, pages={7856–7865} } @article{roux_brooks_yeatts_baynes_2015, title={Skin absorption of six performance amines used in metalworking fluids}, volume={35}, ISSN={["1099-1263"]}, DOI={10.1002/jat.3056}, abstractNote={Abstract}, number={5}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Roux, Lauriane N. and Brooks, James D. and Yeatts, James L. and Baynes, Ronald E.}, year={2015}, month={May}, pages={520–528} } @article{mason_wu_yeatts_baynes_2015, title={Tissue concentrations of sulfamethazine and tetracycline hydrochloride of swine (Sus scrofa domestica) as it relates to withdrawal methods for international export}, volume={71}, ISSN={["1096-0295"]}, DOI={10.1016/j.yrtph.2015.02.013}, abstractNote={The use of water medications is a common practice in the US swine industry to treat and prevent infections in swine herds with minimal labor and without risk of needle breakage. There are concerns that FDA-approved withdrawal times (WDT) may be inadequate for several water medications when exporting pork products to countries where MRLs (maximum residue limits) are lower than US tolerance levels. In this study, withdrawal intervals (WDI) were estimated for pigs when dosed with tetracycline and sulfamethazine in water. The WDI were calculated using the FDA tolerance method (TLM) and a population-based pharmacokinetic method (PopPK). The estimated WDIs (14–16 days using TLM) were similar to the approved WDT of 15 days for sulfamethazine. However, the PopPK method extended WDIs for both sulfamethazine (19–20 days) and tetracycline (12 days) compared to the currently approved WDTs in the U.S. This study also identified potential differences in WDI between weanling and finisher pigs. In conclusion, the TLM may not always provide adequate WDT for foreign export markets especially when MRLs differ from tolerance levels approved for US markets. However, PopPK methods can provide conservative WDIs in situations with considerable variability in medication exposure such as with administration in water.}, number={3}, journal={REGULATORY TOXICOLOGY AND PHARMACOLOGY}, author={Mason, Sharon E. and Wu, Huali and Yeatts, Jim E. and Baynes, Ronald E.}, year={2015}, month={Apr}, pages={590–596} } @article{lindquist_wu_mason_yeatts_brooks_barlow_schill_baynes_2014, title={Tetracycline Residues in Porcine Stomach after Administration via Drinking Water on a Swine Farm}, volume={77}, ISSN={["1944-9097"]}, DOI={10.4315/0362-028x.jfp-13-199}, abstractNote={Tetracycline is a broad-spectrum antibiotic used to treat infections in swine. The maximum residue levels of tetracycline in pork stomach tissue in Russia, Europe, and the United States are 10, 200, and 2,000 ppb, respectively. This difference in accepted safety levels may be the reason why stomach tissues that the United States exports continue to be residue violators in overseas markets. In this study, 30 pigs at two different stages of production (weanling and finisher) were treated with tetracycline at 22 mg/kg of body weight per day for a total of 5 days via a water medicator. Blood samples were collected at 0, 72, 78, 96, and 102 h after the start of medication. The medication was stopped at 120 h, and blood samples were again collected at 126, 144, 168, 192, and 216 h after exposure. Five animals were slaughtered for stomach tissue 0, 24, 48, 96, and 192 h after the drug was flushed from the water line. All blood and tissue samples were analyzed by high-performance liquid chromatography-UV methods. The tetracycline levels in plasma were below the level of detection after the U.S.-labeled withdrawal time of 4 days. The stomach tissue residues averaged 671.72, 330.31, 297.77, 136.36, and 268.08 ppb on withdrawal days 0, 1, 2, 4, and 8, respectively. Using the U.S. Food and Drug Administration tolerance limit method and a population-based pharmacokinetic model with Monte Carlo simulation, a withdrawal interval was estimated. This study demonstrated that tetracycline residues are still detectable in the stomach tissues after the established United States withdrawal time of 4 days. These residue levels may explain why stomach tissues tested in Russia and Europe show positive residues for tetracycline, even though the meat may pass inspection here in the United States prior to export.}, number={1}, journal={JOURNAL OF FOOD PROTECTION}, author={Lindquist, Danielle and Wu, Huali and Mason, Sharon and Yeatts, Jim and Brooks, Jim and Barlow, Beth and Schill, Kaitlyn and Baynes, Ronald}, year={2014}, month={Jan}, pages={122–126} } @article{howard_baynes_brooks_yeatts_bellis_ashwell_routh_o'nan_maltecca_2014, title={The effect of breed and sex on sulfamethazine, enrofloxacin, fenbendazole and flunixin meglumine pharmacokinetic parameters in swine}, volume={37}, ISSN={["1365-2885"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84911423325&partnerID=MN8TOARS}, DOI={10.1111/jvp.12128}, abstractNote={Drug use in livestock has received increased attention due to welfare concerns and food safety. Characterizing heterogeneity in the way swine populations respond to drugs could allow for group‐specific dose or drug recommendations. Our objective was to determine whether drug clearance differs across genetic backgrounds and sex for sulfamethazine, enrofloxacin, fenbendazole and flunixin meglumine. Two sires from each of four breeds were mated to a common sow population. The nursery pigs generated (n = 114) were utilized in a random crossover design. Drugs were administered intravenously and blood collected a minimum of 10 times over 48 h. A non‐compartmental analysis of drug and metabolite plasma concentration vs. time profiles was performed. Within‐drug and metabolite analysis of pharmacokinetic parameters included fixed effects of drug administration date, sex and breed of sire. Breed differences existed for flunixin meglumine (P‐value<0.05; Cl, Vdss) and oxfendazole (P‐value<0.05, AUC0→∞). Sex differences existed for oxfendazole (P‐value < 0.05; Tmax) and sulfamethazine (P‐value < 0.05, Cl). Differences in drug clearance were seen, and future work will determine the degree of additive genetic variation utilizing a larger population.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Howard, J. T. and Baynes, R. E. and Brooks, J. D. and Yeatts, J. L. and Bellis, B. and Ashwell, M. S. and Routh, P. and O'Nan, A. T. and Maltecca, C.}, year={2014}, month={Dec}, pages={531–541} } @article{xu_hughes-oliver_brooks_yeatts_baynes_2013, title={Selection of appropriate training and validation set chemicals for modelling dermal permeability by U-optimal design}, volume={24}, ISSN={1062-936X 1029-046X}, url={http://dx.doi.org/10.1080/1062936X.2012.742458}, DOI={10.1080/1062936x.2012.742458}, abstractNote={Quantitative structure-activity relationship (QSAR) models are being used increasingly in skin permeation studies. The main idea of QSAR modelling is to quantify the relationship between biological activities and chemical properties, and thus to predict the activity of chemical solutes. As a key step, the selection of a representative and structurally diverse training set is critical to the prediction power of a QSAR model. Early QSAR models selected training sets in a subjective way and solutes in the training set were relatively homogenous. More recently, statistical methods such as D-optimal design or space-filling design have been applied but such methods are not always ideal. This paper describes a comprehensive procedure to select training sets from a large candidate set of 4534 solutes. A newly proposed ‘Baynes’ rule’, which is a modification of Lipinski's ‘rule of five’, was used to screen out solutes that were not qualified for the study. U-optimality was used as the selection criterion. A principal component analysis showed that the selected training set was representative of the chemical space. Gas chromatograph amenability was verified. A model built using the training set was shown to have greater predictive power than a model built using a previous dataset [1].}, number={2}, journal={SAR and QSAR in Environmental Research}, publisher={Informa UK Limited}, author={Xu, G. and Hughes-Oliver, J.M. and Brooks, J.D. and Yeatts, J.L. and Baynes, R.E.}, year={2013}, month={Feb}, pages={135–156} } @article{mcphee_anderson_yeatts_mason_barlow_baynes_2011, title={Hot topic: Milk and plasma disposition of thymol following intramammary administration of a phytoceutical mastitis treatment}, volume={94}, ISSN={["1525-3198"]}, DOI={10.3168/jds.2010-3988}, abstractNote={Despite the recent growth of the organic dairy industry, organic producers and veterinarians have limited information when choosing mastitis treatments for animals in organic dairy production. Organic producers commonly administer homeopathic or other plant-based products without having research evaluating the efficacy of these products and using estimated or no withholding times to treat mastitis and other health problems in their herds. In this pilot study, we attempted to identify several active ingredients of Phyto-Mast (Penn Dutch Cow Care, Narvon, PA), a plant-based mastitis treatment used on organic dairy farms, and to quantify the product residue in milk and plasma after intramammary administration. We developed an assay to quantify thymol (one of the active ingredients in Phyto-Mast) in milk and plasma using gas chromatography and mass spectrometry (GC-MS). Thymol is a volatile aromatic compound with antiinflammatory properties. As a model for dairy cows, 5 healthy, lactating alpine dairy goats were given 5 mL of Phyto-Mast per udder half. For 10 d following treatment, we analyzed blood and milk samples for thymol residues using GC-MS. The GC-MS assay was very sensitive for thymol detection, to a concentration of 0.01 μg/mL in plasma. Using thymol as a marker, Phyto-Mast was detectable and quantifiable in plasma beginning with the 15-min posttreatment sample, but was no longer detectable in the 4-h posttreatment sample. Thymol residues were only detected in the 12-h posttreatment milk sample. An inflammatory response was not evident in the udder following phytoceutical administration. Although this study provides information about the elimination of thymol, the product contains several other active chemicals, which may have different pharmacokinetic behaviors. Further analysis and additional study animals will help to determine a milk withholding time for Phyto-Mast. Given the recent growth of the organic dairy industry, understanding the pharmacokinetics of therapeutics used in organic production and developing accurate withholding recommendations will help to ensure milk safety.}, number={4}, journal={JOURNAL OF DAIRY SCIENCE}, author={McPhee, C. S. and Anderson, K. L. and Yeatts, J. L. and Mason, S. E. and Barlow, B. M. and Baynes, R. E.}, year={2011}, month={Apr}, pages={1738–1743} } @article{riviere_brooks_yeatts_koivisto_2010, title={Surfactant Effects on Skin Absorption of Model Organic Chemicals: Implications for Dermal Risk Assessment Studies}, volume={73}, ISSN={["1528-7394"]}, DOI={10.1080/15287391003614026}, abstractNote={Occupational and environmental exposures to chemicals are major potential routes of exposure for direct skin toxicity and for systemic absorption. The majority of these exposures are to complex mixtures, yet most experimental studies to assess topical chemical absorption are conducted neat or in simple aqueous vehicles. A component of many industrial mixtures is surfactants that solubilize ingredients and stabilize mixtures of oily components when present in aqueous vehicles. The purpose of this series of experiments was to use two well-developed experimental techniques to assess how solution interactions present in a pure nonbiological in vitro system (membrane coated fibers, MCF) compare to those seen in a viable ex vivo biological preparation (isolated perfused porcine skin flap, IPPSF). Two widely encountered anionic surfactants, sodium lauryl sulfate (SLS) and linear alkylbenzene sulfonate (LAS), were studied in 10% solutions. The rank orders of absorption were: water: pentachlorophenol (PCP) > 4-nitrophenol (PNP) > parathion > fenthion > simazine > propazine; SLS: PNP > PCP > parathion > simazine > fenthion > propazine; and LAS: PNP > PCP > simazine > parathion > fenthion > propazine. For all penetrants, absorption was greater in SLS compared to LAS mixtures, a finding consistent with smaller micelle sizes seen with SLS. For these low-water-solubility compounds, absorption was greater from aqueous solutions in nearly every case. The inert three-fiber MCF array predicted absorptive fluxes seen in the ex vivo IPPSF, suggesting lack of any biological effects of the surfactants on skin.}, number={11}, journal={JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES}, author={Riviere, Jim E. and Brooks, James D. and Yeatts, James L. and Koivisto, Elisha L.}, year={2010}, pages={725–737} } @article{smith_davis_baynes_yeatts_barlow_riviere_2009, title={Elimination kinetics of tilmicosin following intramammary administration in lactating dairy cattle}, volume={234}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.234.2.245}, DOI={10.2460/javma.234.2.245}, abstractNote={Abstract}, number={2}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Smith, Geof W. and Davis, Jennifer L. and Baynes, Ronald E. and Yeatts, James L. and Barlow, Beth M. and Riviere, Jim E.}, year={2009}, month={Jan}, pages={245–248} } @article{yeatts_baynes_xia_riviere_2008, title={Application of linear solvation energy relationships to a custom-made polyaniline solid-phase microextraction fiber and three commercial fibers}, volume={1188}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2008.02.057}, abstractNote={The term linear solvation energy relationships, LSERs, is considered to be a specific subset of a larger group of thermodynamic relationships called linear free energy relationships. Overall, the LSERs model represents a three-step thermodynamic process. The most recently accepted notation for the LSER equation, proposed by Abraham is given as follows:SP=c+eE+sS+aA+bB+vVwhere SP is any free energy related property of a solute, such as log K, and each term in the equation represents a specific type of chemical interaction. In this work, LSERs were applied to a custom-made polyaniline (PANI) solid-phase microextraction fiber and three commercial fibers immersed in water in order to aid in the assessment of a diverse series of solutes’ partitioning behavior. By experimentally determining the log K for a series of solutes with known solute descriptors (E, S, A, B, and V) and performing multi-linear regression, the unknown system coefficients (e, s, a, b, and v) were obtained. The sign and magnitude of the system coefficients reflect the relative strengths of chemical interactions that affect partitioning between the two phases (fiber and water). The LSER study showed that the system properties having the greatest influence on log K were ease of cavity formation and hydrogen bond donating ability. The differences in dipolarity/polarizability as well as in hydrogen bond accepting ability further showed that all four fibers offer a unique environment for solute partitioning. The PANI fiber may offer greater flexibility in the choice of fibers to use for solid-phase microextraction.}, number={2}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Yeatts, James L., Jr. and Baynes, Ronald E. and Xia, Xin-Rui and Riviere, Jim E.}, year={2008}, month={Apr}, pages={108–117} } @article{vijay_yeatts_riviere_baynes_2007, title={Predicting dermal permeability of biocides in commercial cutting fluids using a LSER approach}, volume={175}, DOI={10.1016/j.toxiet.2007.09.005}, number={1-3}, journal={Toxicology Letters}, author={Vijay, V. and Yeatts, J. L. and Riviere, J. E. and Baynes, R. E.}, year={2007}, pages={34–43} } @article{buur_baynes_yeatts_davidson_defrancesco_2005, title={Analysis of diltiazem in Lipoderm (R) transdermal gel using reversed-phase high-performance liquid chromatography applied to homogenization and stability studies}, volume={38}, ISSN={["0731-7085"]}, DOI={10.1016/j.jpba.2004.11.053}, abstractNote={A simple and novel method for the extraction and quantification of diltiazem hydrochloride was developed and applied to homogenization and stability studies. The method used solid phase extraction coupled with reversed-phase high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Validation showed inter-day recoveries ranging from 84.00 to 96.52% with relative standard deviations ranging from 12.01 to 15.94%. Intra-day recoveries ranged from 67.95 to 106.1% with relative standard deviations less than 5%. The method showed excellent linearity from 50 to 250 mg/ml in undiluted gel (R2 = 0.996). The homogenization study showed good homogenization using both 50 and 100 depression techniques. Diltiazem was stable at a concentration of 246 mg/ml for 30 days and at a concentration of 99.6 mg/ml for 60 days no matter the storage conditions explored in this study.}, number={1}, journal={JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS}, author={Buur, JL and Baynes, RE and Yeatts, JL and Davidson, G and DeFrancesco, TC}, year={2005}, month={Jun}, pages={60–65} } @article{baynes_yeatts_brooks_riviere_2005, title={Pre-treatment effects of trichloroethylene on the dermal absorption of the biocide, triazine}, volume={159}, ISSN={["0378-4274"]}, DOI={10.1016/j.toxlet.2005.05.012}, abstractNote={Triazine is often added to cutting-fluid formulations in the metal-machining industry as a preservative. Trichloroethylene (TCE) is a solvent used for cleaning the cutting fluid or oil from the metal product. The purpose of this study was to examine the effect of TCE on the dermal absorption of triazine in an in vitro flow-through diffusion cell system. Skin sections were dosed topically with aqueous mixtures containing mineral oil or polyethylene glycol (PEG) spiked with 14C-triazine. Some skin sections were simultaneously exposed to TCE while other skin sections were pre-treated with TCE daily for 4 days in vivo and then exposed to these mixtures in vitro. TCE pre-treatment almost doubled triazine permeability, but this pre-treatment had no effect on triazine diffusivity. The pre-treatment effects of TCE on triazine permeability appear to be more important in PEG-based mixtures than in the mineral oil-based mixtures. Simultaneous single exposure to TCE had little or no effect on triazine absorption. TCE absorption was significantly less than triazine absorption; however, cutting fluid additives had a more significant effect on TCE absorption than on triazine absorption. In summary, this study demonstrated that TCE pre-treatment can significantly alter the dermal permeability to triazine, and workers who are chronically exposed to this or similar cleansers may be at increased risk of absorbing related skin irritants.}, number={3}, journal={TOXICOLOGY LETTERS}, author={Baynes, RE and Yeatts, JL and Brooks, JD and Riviere, JE}, year={2005}, month={Dec}, pages={252–260} } @article{smith_gehring_riviere_yeatts_baynes_2004, title={Elimination kinetics of ceftiofur hydrochloride after intramammary administration in lactating dairy cows}, volume={224}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2004.224.1827}, DOI={10.2460/javma.2004.224.1827}, abstractNote={Abstract}, number={11}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Smith, Geof W. and Gehring, Ronette and Riviere, Jim E. and Yeatts, James L. and Baynes, Ronald E.}, year={2004}, month={Jun}, pages={1827–1830} } @article{riviere_baynes_brooks_yeatts_monteiro-riviere_2003, title={Percutaneous absorption of topical N,N-diethyl-m-toluamide (DEET): Effects of exposure variables and coadministered toxicants}, volume={66}, DOI={10.1080/15287390390155796}, number={2}, journal={Journal of Toxicology and Environmental Health. Part A}, author={Riviere, J. E. and Baynes, R. E. and Brooks, J. D. and Yeatts, J. L. and Monteiro-Riviere, N.A.}, year={2003}, pages={133–151} } @article{baynes_yeatts_riviere_2002, title={Analysis of N,N-diethyl-m-toluamide in porcine skin perfusates using solid-phase extraction disks and reversed-phase high-performance liquid chromatography}, volume={780}, ISSN={["1570-0232"]}, DOI={10.1016/S1570-0232(02)00412-9}, abstractNote={N,N-Diethyl-m-toluamide (DEET) is frequently used as an insect repellent by military and civilian populations. Because dermal exposure has resulted in several cases of DEET toxicosis, there is a need to rapidly and reliably determine DEET concentrations in biological matrices. An improved method for the analysis of DEET was developed for determining transdermal diffusion of low levels of DEET following application to an in vitro porcine skin flow-through diffusion cell system. The technical improvement involved the use of disk solid-phase extraction (SPE) instead of packed-bed SPE. The disk SPE method required small volumes of preconditioning, wash, and elution solvent (0.5–1 ml) to extract DEET from perfusate samples containing bovine serum albumin (BSA). The limit of quantitation (LOQ) was estimated as 0.08 μg/ml DEET and recoveries from BSA media samples spiked with DEET ranged from 90.1 to 117% with relative standard deviation (RSD) ranging from 2.0 to 13.1%. This method was used to analyze perfusate samples from skin (n=4) topically exposed to DEET–ethanol formulations. The data from these analyses determined that DEET permeability in porcine skin was 2.55×10−5±0.54×10−5 cm/h.}, number={1}, journal={JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES}, author={Baynes, RE and Yeatts, JL and Riviere, JE}, year={2002}, month={Nov}, pages={45–52} }