Acetylsalicylic acid (ASA), originally trademarked as Aspirin, is a common nonsteroidal anti-inflammatory drug (NSAID) used in human and veterinary medicine to mitigate pain and pyrexia caused by inflammatory processes. There is limited information on the effectiveness of ASA in turkey production. The objective of this study was to investigate the effect of ASA on turkey poults with induced coccidial enteritis. Two experimental trials were conducted. In both trials, the turkeys were divided into four groups: no coccidia + no ASA; no coccidia + ASA (NA); coccidia + no ASA (CN); and coccidia + ASA (CA). In both trials, turkeys in groups CN and CA were given 100× the dose of a commercial turkey coccida vaccine. Starting 48 hr postinoculation and for 7 days, the turkeys from groups NA and CA were given ASA (50 mg/kg per day). For Trial 1, ASA was given via oral gavage twice daily, whereas in Trial 2 (T2), ASA was in the drinking water. Poult weights and cloacal temperatures were recorded daily. Blood was collected daily from two randomly selected birds from each group for biochemical analysis and to assess the serum salicylic acid and nitric oxide (NO) levels. At the end of the trials, tissues were examined histologically, and immune gene expression was evaluated. Coccidia infection was the factor that had most significant influence on the majority of measured parameters. ASA had minimal to no effect on reducing clinical signs, minimizing weight loss, or controlling body temperature. These findings may be due to the rapid elimination of the drug or because sick birds did not consume sufficient ASA. In T2, it was estimated that the CA group poults consumed 31 mg/kg of ASA or less per day. Although the drinking water concentration was calculated to match the total daily intake (50 mg/kg per day), ASA's rapid metabolism meant that continuous low-level ingestion might not have reached the therapeutic plasma threshold achieved by two to three daily bolus doses. Because ASA is rapidly metabolized, a higher total daily dose may be required when provided in drinking water to maintain effective serum concentrations compared with bolus administration. Although the serum NO and tissue gene expression analysis showed that coccidia infection predominantly induces an inflammatory response, the anti-inflammatory effect of ASA administered to birds in the NA or CA groups were nil to minimal. This study highlights the complexity of ASA's effects on turkeys.

This study evaluated the pharmacokinetics of an extended-release buprenorphine formulation (Ethiqa XR) in dogs and explored potential sex differences. Twelve healthy intact beagles (6 males and 6 females) received a single subcutaneous injection of Ethiqa XR (0.2 mg/kg). Blood samples were collected up to 168 h post-administration, and plasma buprenorphine concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital signs, sedation, and nausea scores were recorded. Therapeutic plasma concentrations were sustained for approximately 60-90 h in both sexes, depending on the therapeutic threshold used (0.6 or 1.0 ng/mL). Although no significant differences in pharmacokinetics were detected, drug exposure and elimination were greater in females: median peak plasma buprenorphine concentrations (male: 1.6 ng/mL, female: 2.9 ng/mL); median terminal half-life (male: 36.6 h, female: 24.7 h); area under the curve (AUC 0-12 h) (male: 12.8 h*ng/mL, female: 16.9 h*ng/mL); AUC (0-96 h) (male: 94.4 h*ng/mL, female: 137.7 h*ng/mL). Time to maximum concentrations were 24 h in both sexes. Higher buprenorphine concentrations were associated with decreased body temperature and heart rate in both sexes and positively correlated with nausea and sedation scores, but only in females. Ethiqa XR administration resulted in therapeutic plasma concentrations up to 90 h, suggesting it may be an alternative option for post-operative pain control.

Violative drug residues in animal-derived food are a global food safety concern. Physiologically based pharmacokinetic (PBPK) modeling is a valuable tool for predicting drug residues in edible tissues and determining withdrawal intervals (WDIs). This study aimed to develop a PBPK model for oxytetracycline (OTC) and chlortetracycline (CTC) in swine to determine WDIs based on different regulatory requirements of different countries. The models were calibrated and evaluated with the pharmacokinetic data after oral administration via feed and drinking water collected from the Food Animal Residue Avoidance Databank (FARAD). The models can accurately capture the observed kinetics in plasma and edible tissues (liver, muscle, kidney, and fat), and most of the model predictions were within a 3-fold factor of observed data (87.9% for OTC and 88.9% for CTC). WDIs of OTC and CTC were determined using the population PBPK models based on maximum residue limits (MRLs) from 13 countries or regions under the label dosage regimens. The models were converted to a web-based PBPK dashboard. The models are a useful tool for predicting tissue residues and estimating WDIs based on different MRLs across countries, thereby supporting food safety assessment and international trade of meat products derived from swine treated with OTC and CTC.

IntroductionFlunixin meglumine is a non-steroidal anti-inflammatory drug (NSAID) commonly used extra-label in goats, necessitating the determination of an extended withdrawal interval (WDI) to minimize the risk of violative residues at slaughter. Current U.S. Food and Drug Administration (FDA) guidance estimates WDIs using univariate ordinary least squares (OLS) regression applied to concentrations at or above the limit of detection (LOD), defining the WDI as the time at which the upper bound of the 95% confidence interval for the 99% quantile falls below a specified tolerance. However, residue concentrations measured across multiple tissues from the same animal may be correlated, and excluding observations below the LOD may distort estimates by removing information from the terminal depletion phase.Materials and methodsWe propose a multivariate linear regression (MvLR) framework that jointly models inter-tissue dependence while accommodating left-censored observations. Regression parameters are estimated using OLS and generalized least squares (GLS) under the uncensored MvLR model, and via an expectation conditional-maximization (ECM) algorithm under a censored MvLR formulation. Withdrawal intervals are computed using the multivariate t-distribution to obtain the upper limit of the 95% confidence interval for the 99% quantile across tissues. The methods are illustrated using tissue-residue data from 20 Boer goats administered flunixin meglumine at 2.2 mg/kg, with five animals euthanized at each of four post-treatment time points (24, 48, 72, and 96 h) and are further evaluated in a simulation study.ResultsThe simulation results indicate that the ECM-based censored MvLR approach yields stable parameter estimation and reliable WDI inference in the presence of censoring. Applying this framework to the goat residue data suggests that a withdrawal interval of at least 10 days is recommended to ensure that residues across all tissues fall below conservative safety thresholds.DiscussionThese findings suggest that a multivariate censored modeling framework can improve WDI estimation by accounting for inter-tissue correlation and incorporating observations below the LOD, addressing key limitations of current univariate FDA-style approaches.

Objective:To characterize the pharmacokinetics in blood and plasma and determine residue profiles of IV-administered methylene blue (MB) to support withdrawal interval (WDI) recommendations. Methods:This was a prospective, nonrandomized pharmacokinetic and residue study using noncompartmental analysis. The study took place from May 2023 through December 2023. Eight Holstein-cross cattle (4 steers, 2 heifers, 2 cows; ages, 5.4 to 6 months for steers and heifers and approx 5.5 years for cows; mean weights, 198 to 495 kg) were housed individually with controlled diet and water access. Animals received 6 mg/kg of compounded 2.5% MB IV. Blood and plasma samples were collected for 72 hours. Milk samples were collected twice daily. At 3 and 6 days after dose, tissue samples were collected after euthanasia. Drug concentrations were measured via UPLC-MS-MS assay. Withdrawal interval estimates used modified FDA tolerance limits and European Medicines Agency time-to-safe-concentration methods. Results:MB was rapidly eliminated, with plasma concentrations below the limit of quantification by 12 hours and blood by 24 hours. No residues were detected in any tissues at sampling times. Milk concentrations were detected at approximately 12 hours (0.084 ± 0.04 µg/mL). Milk WDI estimates were 89 hours and approximately 5 days based on the modified FDA and European Medicines Agency approaches, respectively. Conclusions:IV MB at 6 mg/kg in cattle was well tolerated, eliminated rapidly, and produced no tissue residues at 3 or 6 days. Clinical Relevance:Data suggest that compounded MB at this dose and route as an emergency antidote poses no food safety concerns provided WDIs of 5 days for milk and 6 days for meat are recommended to producers.

Mastitis is the most burdensome concern for the dairy cattle industry. Antimicrobials are often prophylactically administered to dairy cows at dry-off to reduce the risk of intramammary infection during the dry period and subsequent lactation. Mastitis incidence has increased in dairy heifers after calving, leading to extralabel drug use of various dry cow products, including intramammary ceftiofur hydrochloride. However, the pharmacokinetics and efficacy of this application have yet to be studied. This study aimed to compare the pharmacokinetics and efficacy following no treatment, a non-antimicrobial teat sealant, or a single dose of intramammary ceftiofur given at 21 or 14 days before expected calving. We hypothesized that milk collected following dosing would contain drug residues below the FDA tolerance of 100 ng/mL by calving, and heifers within the ceftiofur treatment groups would have lower somatic cell counts (SCCs) than heifers in the teat sealant and nontreatment control groups. Following treatment or no treatment of 24 prepartum heifers, milk samples were collected until 21 days after calving. Somatic cell counts and ceftiofur concentrations were assessed utilizing a cell counter and UPLC/MS detection, respectively. Ceftiofur administration did not significantly reduce SCCs compared to other groups by days 7, 14, or 21. For heifers treated 14 and 21 days prior to calving, milk had a maximum ceftiofur concentration of 8.14 ± 6.24 and 4.20 ± 5.07 ng/mL 48 h into lactation, respectively. The minimal ceftiofur concentrations in milk collected from these heifers indicate that administration of ceftiofur 14 or 21 days before calving is unlikely to lead to violative residues. However, it is essential that regional regulations regarding the use of ceftiofur are adhered to.

Prophylactic and perioperative use of antibiotics is common prior to abdominal surgery in cattle for minimizing the risk of postoperative infections. Yet, there is little information on drug concentrations at sites of potential infections following surgical procedures. The objective of this study was to compare the concentrations in the plasma, peritoneal fluid, and interstitial fluid of ampicillin trihydrate in cattle. In a randomized design, ampicillin trihydrate, a β-lactam antibiotic, was administered to 12 healthy Holstein-Friesian steers intraoperatively via intraperitoneal (IP; n = 6) or intramuscular (IM; n = 6) injection in the cervical neck muscles at 11 mg/kg for both groups. For IP administration, ampicillin trihydrate was deposited into the abdominal cavity following an incision in the right paralumbar fossa. Steers in the IM group were administered ampicillin prior to surgical closure. Peritoneal fluid and interstitial fluid were collected using ultrafiltration probes. IP administration achieved higher concentrations in peritoneal fluid as compared to IM administration. Maximum plasma concentrations were significantly higher following IP administration (3.11 ± 2.5 μg/mL; p < 0.004) compared to the IM group (0.05 ± 10.9 μg/mL). Despite high peritoneal fluid concentrations of ampicillin, the variability in critical pharmacokinetic parameters following IP administration raises concerns about its therapeutic reliability. The correlation between intraperitoneal drug concentrations and clinical efficacy warrants further investigation.

The objective of the study was to evaluate the pharmacokinetics of flunixin meglumine of intravenous (IV) and transdermal (TD) flunixin meglumine administration on different coat types (wool vs. hair) in 12 healthy sheep. Polled dorset (wool) sheep (n = 6) and katahdin (hair) sheep (n = 6) received 2.2 mg/kg IV and 3.3 mg/kg TD with a 10-day washout period between treatments. Plasma samples were obtained for 96 h following both IV and TD administration, respectively. Flunixin concentrations were quantified by use of high-performance liquid chromatography with mass spectrometry, and PK parameters were derived using different modeling techniques. A population non-linear mixed effect model showed that coat type has a significant effect on the absorption rate following TD administration. The mean bioavailability of TD flunixin was not significantly different (48.76% ± 17.49% and 36.61% ± 4.33%; p = 0.093) in wool and hair sheep, respectively. Maximum plasma concentrations following TD administration were higher in wool sheep (1.57 μg/mL; range, 0.6-3.41 μg/mL) compared to hair sheep (0.57 μg/mL; range, 0.36-0.83 μg/mL). The PK results provide further support for clinical studies to examine the efficacy of TD flunixin in different breeds of sheep.

Objective:To determine the pharmacokinetics of a single dose of flunixin transdermal formulation in American bullfrogs (Lithobates catesbeianus). Methods:Clinically healthy, purpose-bred adult bullfrogs housed at the North Carolina State University College of Veterinary Medicine were enrolled in a sparse-sampling population study. Frogs were administered 3.3 mg/kg transdermal flunixin meglumine (Banamine Transdermal; Merck Animal Health) on the dorsum via micropipette under manual restraint in July of 2022. Frogs were maintained in individual containers out of water for 4 hours and randomly assigned to 2 of the following venipuncture time points: 1, 2, 4, 8, 12, or 24 hours, with 7 frogs sampled per time point. Blood was collected from the popliteal sinus. Ultra performance liquid chromatography-tandem mass spectrometry was used to determine plasma flunixin concentrations. Data were analyzed using noncompartmental analysis. Results:Flunixin was detected in all samples collected from 21 bullfrogs (9 males and 12 females). A mean peak plasma concentration of 2.39 µg/mL was reached between 1 and 2 hours. The elimination half-life was 15.0 hours. Plasma concentrations were similar across individuals at 1, 2, and 4 hours (range at 1 and 2 hours, 2.32 to 2.55 µg/mL) but were variable at 8, 12, and 24 hours (range at 24 hours, 0.16 to 1.79 µg/mL). Mucus and/or epithelial loss was noted at the drug application site in 18 of 21 frogs. No additional clinical signs or mortality occurred. Conclusions:Transdermal flunixin was systemically absorbed, and plasma concentrations exceeded established therapeutic ranges in other species. Most frogs developed mild cutaneous lesions. Clinical Relevance:Transdermal flunixin was detected in plasma for 24 hours; however, variability in plasma concentrations over time and topical side effects may limit its use.

Bed bugs have become resistant to traditional insecticides, and the demand for effective drugs to eradicate bed bugs on poultry farms (especially table-egg layer) and breeder farms (especially broiler breeders) is growing. Fluralaner has been shown to be effective in treating bed bug infestation in poultry. However, there is no product containing fluralaner labeled for use in chickens in the United States. In the present study, we prepared medicated drinking water using fluralaner dog chews (Bravecto®) and diethylene glycol monoethyl ether (Transcutol V). The present study aimed to determine the plasma pharmacokinetic profile and residues in liver as well as any adverse effects related to drug administration. All chickens were orally treated with fluralaner via medicated drinking water including 0.2 % (V/V) Transcutol V for 6 hours. The fluralaner dosage regimen was 0.5 mg/kg/day, twice, 7 days apart. Sparse blood collection was conducted after the first dose and tissue collection was performed the day after the second dose. The fluralaner concentrations in plasma and liver were determined using Ultra Performance Liquid Chromatography with tandem Mass Spectrometry detection (UPLC/MS/MS). Fluralaner was dissolved completely in drinking water including 0.2 % (V/V) Transcutol V with 98 % recovery with some degradation of fluralaner confirmed over time. The highest fluralaner concentration (0.56 µg/mL) in plasma was observed 24 hours after removing the first dose. Fluralaner concentrations in plasma exceeded the 50-90 % lethal concentrations of bed bugs for 168 hours following the onset of the first dose. The mean fluralaner concentration detected in the liver was 1.25 µg/g at 21 hours after removing the second dose. No visual adverse effects were observed during the entirety of the study. Enlarged kidneys were observed by gross necropsy and mild multifocal, small aggregations of lymphocytes in the parenchyma and mineralization of a few tubules in kidneys were found on histopathological examination. However, it was unclear these findings were related to drug administration. This dosing method might be helpful in controlling bed bug infestations in poultry facilities.

Ponazuril (Marquis®) is a triazine based antiprotozoal medication labeled to treat equine protozoal myeloencephalitis in the United States. Ponazuril is often used in an extra-label manner to treat coccidiosis in piglets, but tissue residue data is limited. In this study, piglets were given a single oral dose of 5 mg/kg ponazuril. Piglets (n = 5) were euthanized at eleven timepoints (0, 15, 28, 43, 57, 71, 85, 99, 113, 127, and 141 days) with tissue sample collection and chromatographic analysis. The maximum residue limit (MRL) values established by the European Medicines Agency (EMA) and our laboratory limits of detection (LOD) were used as the safe levels to estimate withdrawal intervals (WDIs). Based on MRL values, the WDIs for liver, kidney, muscle and fat were approximately 72 days, 176 days, 90 days and 81 days, respectively. As this is extra-label use, any residue detected will be a violation. If the LOD was used instead of the MRL values, the WDIs would extend to as much as 130 days (liver), 270 days (kidney), 105 days (muscle), and 101 days (fat).

Physiologically based pharmacokinetic (PBPK) models are commonly used in human drug discovery and development and human health risk assessment of environmental chemicals. One emerging application of PBPK models is to predict tissue residues and withdrawal times of drugs in food animals, which is important for human food safety assessment of animal-derived food products, such as meat, milk, and eggs. This review summarizes existing guidelines to establish the regulatory agency approved label withdrawal period and available pharmacometric methods to predict extralabel withdrawal times, with a focus on PBPK modeling. We conducted a comprehensive literature search on existing PBPK models in food animals. Two hundred thirteen PBPK models in different food animal species (e.g., cattle, swine, sheep, goats, and chickens) from 113 publications were identified. The general procedure to build a PBPK model for a drug in food animals to predict withdrawal times is summarized. Differences in PBPK modeling between humans and food animals and between different food animal species are discussed. Novel uses of PBPK models to predict extralabel withdrawal times are illustrated with recent case studies from the Food Animal Residue Avoidance Databank (FARAD). Recent advances and challenges in PBPK modeling in food animals are discussed, followed by our future perspectives on how to develop more robust PBPK models for food animals to address the safety assessment of animal-derived food products.

Flunixin meglumine is a nonsteroidal anti-inflammatory drug (NSAID). Banamine Transdermal is a pour-on formulation of flunixin approved for pain control in beef and dairy cattle, but not for calves and some classes of dairy cattle or swine. Violative flunixin residues in edible tissues in cattle and swine have been reported and are usually attributed to non-compliant drug use or failure to observe an appropriate withdrawal time. This project aimed to develop a physiologically based pharmacokinetic (PBPK) model for flunixin in cattle and swine to predict withdrawal intervals (WDI) after exposures to different therapeutic regimens of Banamine Transdermal. Due to the lack of comprehensive skin physiological data in cattle, the model was initially developed for swine and then adapted for cattle. Monte Carlo simulation was employed for population variability analysis. The model predicted WDIs were rounded to 1 and 2 d for liver and muscle in cattle, respectively, under FDA tolerance levels, while under EU maximum residue limits, the WDIs were rounded to 1, 3, 2, and 2 d for liver, kidney, muscle, and fat, respectively, following a labeled single transdermal 3.3 mg/kg dose in cattle. The model was converted into a user-friendly interactive PBPK (iPBPK) interface. This study reports the first transdermal absorption model for drugs in cattle. This iPBPK model provides a scientifically based tool for the prediction of WDIs in cattle and swine administered with flunixin in an extra-label manner, especially by the transdermal route.

The food animal sector’s use of antimicrobials is heavily critiqued for its role in allowing resistance to develop against critically important antimicrobials in human health. The WHO recommends using lower tier antimicrobials such as florfenicol for disease treatment. The primary objective of this study was to assess the differences in resistance profiles of enteric microbes following administration of florfenicol to steers using both FDA-approved dosing regimens and two different detection methods. Our hypothesis was that we would identify an increased prevalence of resistance in the steers administered the repeated, lower dose of florfenicol; additionally, we hypothesized resistance profiles would be similar between both detection methods. Twelve steers were administered either two intramuscular (20 mg/kg q 48 h; n = 6) or a single subcutaneous dose (40 mg/kg, n = 6). Fecal samples were collected for 38 days, and E. coli and Enterococcus were isolated and tested for resistance. Fecal samples were submitted for metagenomic sequencing analysis. Metagenomics revealed genes conferring resistance to aminoglycosides as the most abundant drug class. Most multidrug resistance genes contained phenicols. The genotypic and phenotypic patterns of resistance were not similar between drug classes. Observed increases in resistant isolates and relative abundance of resistance genes peaked after drug administration and returned to baseline by the end of the sampling period. The use of a “lower tier” antimicrobial, such as florfenicol, may cause an increased amount of resistance to critically important antimicrobials for a brief period, but these changes largely resolve by the end of the drug withdrawal period.

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.

Parasitic infections in dairy cattle reduce herd immunity, milk production, and conception rates. This leads to higher production costs, compromised animal welfare, and increased interest in extralabel drug use. The extralabel use of anthelmintics poses food safety risks for consumers since appropriate withdrawal intervals in milk have yet to be established. Although topical eprinomectin has no milk withdrawal time, more research is needed to determine the residues present in milk after subcutaneous administration. This study aimed to characterize the pharmacokinetics of injectable eprinomectin in dry dairy cows. We hypothesized that, when given at the labeled dose, eprinomectin residues in dry dairy cattle would be below the FDA milk tolerance at the onset of lactation. Plasma was collected daily from 13 mature dairy cattle for 7 days postadministration, followed by periodic samples for 90 days. After calving, milk was collected daily until 90 days. Eprinomectin concentrations were measured using HPLC-fluorescence detection. The maximum eprinomectin concentration in plasma and milk was approximately 36 ng/mL 43 h after administration and 3 ng/mL at the onset of lactation, respectively. The low eprinomectin levels in milk collected from these lactating dairy cattle suggest that administering eprinomectin at dry-off is unlikely to result in violative residues. However, subcutaneous eprinomectin in lactating dairy cattle would be hard to justify unless there is evidence that the approved topical formulation is clinically ineffective.

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.

AbstractBackgroundPharmacological 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.ObjectiveEvaluate the disposition of ceftiofur hydrochloride administered intramammary in diseased and nondiseased quarters. Whole milk and ultrafiltrate sampling techniques were compared.AnimalsTen 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.MethodsUltrafiltration 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.ResultsThe 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 ImportanceSignificant 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.

Firefighter occupational exposures were categorized as a class 1 (known) carcinogen by the International Agency for Research on Cancer in 2022. As a result, firefighters have become heavily focused on identifying effective and easy to implement decontamination strategies to reduce their chemical exposures. Skin decontamination using wipes post-exposure is one decontamination strategy that every firefighter has available to them. However, firefighters have expressed concerns over the ingredients in the wipe solution increasing dermal absorption. The goal of this study was to determine if the ingredients in skin decontamination wipe solution had any enhancement effect on the dermal absorption of phenanthrene. To determine any enhancement effects, the additive solution of four skin decontamination wipe products was applied to porcine skin 15 min after chemical dosing. The absorption of phenanthrene was tested in vitro using a flow-through diffusion cell system over eight hours. The wipe solution effects on dermal absorption were determined by measuring multiple absorption characteristics including cumulative absorption (µg/cm2), absorption efficiency (% dose absorbed), lag time (minutes), flux (µg/cm2/h), diffusivity (cm2/h), and permeability (cm/h). No penetration enhancement effects were observed in any of the skin decontamination wipe solutions tested; rather, all wipe solutions decreased the absorption of phenanthrene. Slight differences in cumulative absorption among two pairings of skin decontamination wipe solutions, wipes 1 and 3 vs. wipes 2 and 4, were observed, indicating that some ingredients may impact dermal absorption. These findings show that firefighters should continue using skin decontamination wipes to reduce their dermal exposures to fireground contaminants with little concern of increasing the absorption of phenanthrene.