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The objective of this study was to assess the impact of the vehicle of administration and the prandial state of post weaning piglets on the indices of therapeutic efficacy for different broad-spectrum antibiotic/pathogen combinations. Pharmacokinetic data were retrieved from previous studies, in which we orally administered oxytetracycline (OTC), fosfomycin (FOS), or amoxicillin (AMX) according to the following treatments: dissolved in soft water to fasted or non-fasted piglets, dissolved in hard water to fasted or non-fasted piglets, and mixed with feed. Minimum inhibitory concentration (MIC) values for susceptible strains of bacteria causing swine diseases were obtained from the database of European Committee on Antimicrobial Susceptibility Testing (EUCAST) for each antibiotic. Pharmacokinetic/pharmacodynamic (PK/PD) indices of therapeutic efficacy-drug exposure over the dosing interval (fAUC/MIC) for OTC and FOS; time that free drug concentration remains above MIC (%fT>MIC) for AMX-were calculated for each antibiotic/pathogen combination under each treatment. After all OTC and in-feed FOS and AMX treatments, the indices of therapeutic efficacy were below the target value for all the study microorganisms. When FOS or AMX were delivered dissolved in soft or hard water, the indices were above the target value over which therapeutic efficacy would be expected for Escherichia coli treated with FOS and, Glaesserella parasuis, Pasteurella multocida, and Actinobacillus pleuropneumoniae treated with AMX. The prandial state of piglets showed no influence on the indices of therapeutic efficacy. Pharmacokinetic profiles of broad-spectrum antibiotics, specifically the ability to achieve target concentrations, may be largely reduced due to drug interactions with components present in feed or water resulting in a discrepancy with PK/PD principles of prudent and responsible use of antibiotics., (© 2024 John Wiley & Sons Ltd.)

Feed and water components may interact with drugs and affect their dissolution and bioavailability. The impact of the vehicle of administration (feed and water) and the prandial condition of weaner piglets on amoxicillin´s oral bioavailability was evaluated. First, amoxicillin's in vitro dissolution and stability in purified, soft, and hard water, as well as release kinetics from feed in simulated gastric and intestinal media were assessed. Then, pharmacokinetic parameters and bioavailability were determined in fasted and fed pigs using soft water, hard water, or feed as vehicles of administration following a balanced incomplete block design. Amoxicillin showed similar dissolution profiles in soft and hard water, distinct from the dissolution profile obtained with purified water. Complete dissolution was only achieved in purified water, and merely reached 50% in soft or hard water. Once dissolved, antibiotic concentrations decreased by around 20% after 24 h in all solutions. Korsmeyer-Peppas model best described amoxicillin release from feed in simulated gastric and intestinal media. Feed considerably reduced antibiotic dissolution in both simulated media. In vivo, amoxicillin exhibited significantly higher bioavailability when delivered via water to fasted than to fed animals, while in-feed administration yielded the lowest values. All treatments showed a similar rate of drug absorption. In conclusion, we demonstrated that water and feed components, as well as feed present in gastrointestinal tract of piglets decrease amoxicillin´s oral bioavailability. Therefore, the use of oral amoxicillin as a broad-spectrum antibiotic to treat systemic infections in pigs should be thoroughly revised., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To describe citrullinemia profiles during the weaning transition and correlate citrulline production with stress and growth in a commercial pig farm., Animals: 240 healthy piglets of homogenous weight, weaned from second and third parity sows, were selected at weaning and subjected to the farm's routine management practices in May to July 2020 and May to July 2021., Procedures: Piglets were weighed at weaning, then 15 and 49 days later in order to calculate daily weight gain during the first 15 and 49 days after weaning. Blood samples were collected from each piglet to determine citrulline and cortisol profiles during the early postweaning period., Results: Citrullinemia decreased dramatically during the first week postweaning and then increased progressively to reach preweaning values by 15 days postweaning. Citrulline production during the first 2 weeks postweaning was negatively correlated with cortisol production (r: -0.2949) and positively correlated with mean daily weight gain during the first 15 (ρ: 0.5450) and 49 (ρ: 0.6603) days postweaning., Clinical Relevance: Citrullinemia profile of piglets during the early postweaning period showed a temporal negative impact of stress (assessed by plasmatic cortisol levels) on intestinal enterocytes' mass and function, which resulted in a lower average daily weight gain. We demonstrated that a single biomarker, plasmatic citrulline, is useful to describe intestinal metabolism during the early postweaning period and that the greater the citrulline production during the first days after weaning, the higher the weight gain during the entire postweaning period.

The incorporation of natural essential oils to the pigs' diet in intensive production systems is a potential tool to improve gut health and prevent infections without using antibiotics. Nevertheless, different products, even containing the same compounds, coming from the same botanical species, may exert dissimilar biological effects due differences in the technological processes by which they are produced and preserved. For this reason, suitability of a given product based on natural extracts, intended for swine production must be thoroughly evaluated. In the present study, we assessed the effects of three additives containing oregano (Lippia origanoides) essential oil, alone or in combination with clover (Eugenia caryophillata) essential oil, with or without being microencapsulated, on gastrointestinal health and on some performance parameters in a commercial pig production farm. Recently weaned piglets were randomly divided in four groups, and basal diet or essential oil-supplemented diet (OCE; MOCE; MOE) was randomly assigned to each of the groups from weaning to finishing. Blood samples were collected at pre-established days after weaning. Intestinal sampling took place at 42 and 72 days of age. Pigs consuming the supplemented diets showed higher intestinal metabolic activity during the post-weaning period, decreasing the impact of weaning stress on enterocytes' metabolism. Intestinal barrier function was not affected in pigs consuming microencapsulated products. All treated groups showed improved intestinal architecture, increased digestive enzymes activity and caecal VFA concentrations. The incorporation of the dietary essential oils products brought beneficial effects on gastrointestinal health that were reflected in improved performance parameters., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Feed and drinking water are the most frequently used vehicles for administration of antibiotics in intensive pig production. Interactions of drugs with feed and water components may affect dissolution and bioavailability. Therefore, antibiotic formulations should be tested in order to assure their suitability for oral use. In this study, an oral fosfomycin (FOS) formulation was evaluated considering dissolution in water (soft and hard), release kinetics from feed in simulated gastrointestinal fluids and bioavailability after oral administration blended into feed or dissolved in water (soft and hard), to fed and fasted piglets. FOS reached immediate dissolution in soft and hard water. The presence of feed significantly decreased antibiotic dissolution in simulated intestinal medium. Bioavailability was lower when feed was used as a vehicle for FOS administration than when the drug was dissolved in water (soft or hard). The fed or fasted condition of piglets did not affect bioavailability. Probably, FOS interactions with feed components alter its dissolution in the gastrointestinal tract, and only a fraction of the dose would be available for absorption. This information must be considered to support decisions on eligibility of antibiotic pharmaceutical formulations and the vehicle for their administration in order to pursue a responsible use of antibiotics., (© 2021 John Wiley & Sons Ltd.)

Weaning is a challenging stage of pig farming. Animals undergo environmental, social and dietary changes leading to weaning stress syndrome. In order to compensate for the detrimental effects of weaning stress, antibiotics and natural extracts are used as feed additives, sometimes without fully understanding the interactions between them or even with low concentrations of mycotoxins that are frequently present in feed. The aim of this study was to evaluate the effect of fosfomycin (FOS), Cynara scolymus extract (CSE), deoxynivalenol (DON) and their combined administration on intestinal health of weaned piglets. The experiment was designed as a 2 × 2 × 2 factorial arrangement with 3 factors (FOS, CSE and DON treatments), 2 levels each (presence and absence) and 3 repeats. Weaned piglets ( n  = 24) were randomly divided in groups to receive the different treatments, namely DON administered in diet (50 μg/kg BW), FOS administered into the drinking water (30 mg/kg BW), CSE administered in diet (15 mg/kg BW) and all their combinations. After 15 d, the animals were euthanized and gastrointestinal tract samples were immediately taken to evaluate gastrointestinal pH, Enterobacteriaceae to lactic acid bacteria (E:L) ratio, volatile fatty acid (VFA) concentrations, disaccharidase (lactase, sucrase and maltase) activity, histology (intestinal absorptive area [IAA] and goblet cells count) and mucus ability to adhere pathogenic Escherichia coli . From our results, FOS and CSE treatments, individually or combined, produced a lower E:L ratio, an enhanced production of butyrate, increased disaccharidase activity (particularly maltase), and a greater IAA and goblet cells count along with an increase in pathogenic bacteria adherence to intestinal mucus. Deoxynivalenol did not show interactions with the other factors and its administration produced decreases on VFA, disaccharidase activity and goblet cells count. In conclusion, weaning piglets receiving diets containing FOS, CSE or both exhibited evident beneficial intestinal effects compared to animals receiving diets free from these compounds. On the contrary, the presence of DON at sub-toxic concentrations produced detrimental effects on intestinal health. The knowledge of the physiological and pathological gut changes produced by these compounds contributes to understand their potential productive consequences., (© 2019 Chinese Association of Animal Science and Veterinary Medicine. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Water hardness is a critical factor that affects oxytetracycline dissolution by chelation with cations. These interactions may lead to impaired dosing and consequently decrease absorption. Moreover, feed present in gastrointestinal tract may interact with antibiotic and alter pharmacokinetic parameters. In the present study, dissolution profiles of an oxytetracycline veterinary formulation were assessed in purified, soft and hard water. Furthermore, oxytetracycline absolute bioavailability, after oral administration of the drug dissolved in soft or hard water, was evaluated in fed and fasted piglets. A maximum dissolution of 86% and 80% was obtained in soft and hard water, respectively, while in purified water dissolution was complete. Results from in vivo study reconfirmed oxytetracycline's very low oral bioavailability. The greatest values were attained when antibiotic was dissolved in soft water and in fasted animals. Statistically significant lower absolute bioavailability was achieved when hard water was used and/or animals were fed. Moreover, Cmax attained in all treatments was lower than MIC90 of most important swine pathogens. For these reasons, the oral use of OTC formulations, that have demonstrated low oral bioavailability, should be avoided to treat systemic diseases in pigs., (© 2019 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Fosfomycin (FOS) is an antibiotic used, mostly in Latin America, for the treatment of lung and enteric infections of pigs. Intracellular fluids of enterocytes can act as biophase for Lawsonia intracellularis, the causative agent of porcine proliferative enteropathy (PPE). The aim of this study was to determine whether the presence of L. intracellularis in the enterocytes modifies FOS penetration. Eight healthy pigs in growth-finishing stage were used to produce healthy (group A) and L. intracellularis-colonized (group B) intestinal explants. For both groups, treatment consisted of a 580 μg/ml concentration of calcium FOS, which was added to each explant (0.5-6 hr). For group B, the Enterisol Ileitis ® vaccine was used as source of the micro-organism. Previously to the assay, the time necessary for L. intracellularis to colonize the enterocytes was defined. Also, a PCR protocol was optimized to determine the presence of the pathogen in the explants. There were nonstatistical differences for the penetration of the antibiotic into healthy and L. intracellularis-colonized enterocytes. MIC 90 of FOS for L. intracellularis is unknown; nevertheless, MIC 90 of various antibiotics ranges between 0.125 and 128 μg/ml. FOS reaches inside the enterocyte concentrations which surpass the MICs 90 of other antibiotics that also act by the inhibition of cell wall synthesis; however, further studies should be carried out to determine fosfomycin MIC 90 for L. intracellularis to discern the usefulness of this antibiotic in the treatment of PPE., (© 2018 John Wiley & Sons Ltd.)

Fosfomycin is a broad-spectrum bactericidal antibiotic widely used in pig farms for the treatment of a wide variety of bacterial infections. In this study, the elimination of disodium fosfomycin in colostrum/milk of the sow and the impact of this antibiotic on the microbiota and intestinal morpho-physiology of suckling piglets were analyzed. The average amount of fosfomycin eliminated in colostrum (after administration of 15 mg/kg IM) during the first 10 hr postpartum was 0.85 μg/ml, and the mean residual amount ingested by the piglets was 0.26 mg/kg. The elimination profile of fosfomycin concentrations in colostrum occurs at a time of profound changes in the morpho-physiology of the gastrointestinal tract of the piglet. However, the studied concentrations did not produce imbalances on the microbiota or on the morpho-physiology of the gastrointestinal tract of the piglet. Concentrations of fosfomycin were maintained in the mammary gland above the MIC for more than 8 hr for pathogenic bacteria of productive importance. This would indicate that fosfomycin may be considered safe for the specific treatment of bacterial infectious processes in sows during the peri- and postpartum period. This first study with disodium fosfomycin stimulates awareness in the proper use of antimicrobials at farrowing., (© 2018 John Wiley & Sons Ltd.)

The ability to adsorb zearalenone by five strain of lactic acid bacteria was evaluated: four strains of Lactobacillus spp. isolated from pig rectal swabs and one commercial strain (Lactobacillus rhamnosus). Several factors affecting the adsorption capacity were evaluated in order to improve the adsorption of the mycotoxin by bacteria. The stability of the zearalenone-bacteria complex was analyzed. In every case, bacterial adsorption capacity was higher than 40.0%. The strain showing the highest adsorption (68.2%) was selected for the following steps of this research. The adsorption percentages obtained after processing 6.5 and 7.5mL MRS broth were 57.40%+3.53 and 64.46%+0.76, respectively. The stability of zearalenone-bacteria complex was evaluated by successively rinsing. In the first rinsing step 42.26%+0.414 was still bound. In the second rinsing step 25.12%+0.664 was still bound, whereas 15.82%+0.675 remained in the pellet after the third rinse. Results obtained demonstrated that Lactic Acid Bacteria has capacity to adsorb zearalenone. Finally adsorption was increased using a higher volume of initial broth. These results could be used to design a new lyophilized powder for detoxification, using lactic acid bacteria as potential zearalenone adsorbents., (Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.)

The objective of this study was to document the effect of social ranking on the internal exposure of pigs to an antibiotic (fosfomycin) administered either in food or in drinking water. Signs of aggression were recorded at the feeder and drinker. The interindividual variability explained by the social rank was even greater when the test antibiotic was given in food despite the fact that the water consumption was less variable than the food intake. The range of plasma concentrations after administration of fosfomycin either in food or drinking water leads to a number of pigs in the treated group being exposed to rather low and highly variable concentrations of fosfomycin and not able to maintain adequate plasma concentrations above the typical minimum inhibitory concentration (MIC). Social rank clearly influences the level of exposure of pigs to fosfomycin both in food and drinking. However, its administration in drinking water is likely to be the best option to optimize antibiotic efficacy., (Copyright © 2013. Published by Elsevier Ltd.)

Six single-flow continuous cultures were used to study the effects of the mycotoxins patulin (PAT) and zearalenone (ZEN) alone or in combination on rumen microbial fermentation. In each of the four 7-d periods, the fermenters were supplemented in a 2 × 3 factorial arrangement with two levels of PAT (0 and 20 mg/l) and three levels of ZEN (0, 5 and 10 mg/l). The treatments did not affect the apparent and true digestibility of organic matter. PAT alone decreased the digestibility of neutral detergent fibre (NDF) and acid detergent fibre (ADF) (p < 0.01), but in the presence of 5 or 10 mg/l of ZEN, there were no effects of PAT. In contrast, the digestibility of NDF and ADF was decreased at 10 mg/l of ZEN in the absence of PAT (p < 0.05). The pH of the fermenters increased after 2 and 3 d of PAT treatment (p < 0.01). PAT decreased the concentration of total volatile acids (VFA), the molar proportion of acetate and the acetate:proportionate ratio (p < 0.01). The molar concentrations of other VFA were unchanged. Ammonia N (NH3-N) flow increased (p < 0.05) and there was a tendency to a higher NH3-N concentration (p < 0.1) in fermenters with PAT. Total N, non-ammonia N and bacterial N as well as efficiency of microbial protein synthesis and efficiency of N utilisation were not affected by treatments. PAT was nearly completely degraded during incubation. The mean recovery of ZEN, α-zearalenol and β-zearalenol expressed as a proportion of administered ZEN was less than 50% in effluents from fermenters receiving only ZEN and ZEN plus PAT, respectively. With exception of fibre digestion, the co-administration of PAT and ZEN did not elicit interaction effects on most measured parameters of rumen metabolism.

Fosfomycin (FOS) is a natural bactericidal broad-spectrum antibiotic which acts on proliferating bacteria by inhibiting cell wall and early murein/peptidoglycan synthesis. Bactericidal activity is evident against Gram positive and Gram negative bacteria and can also act synergistically with other antibiotics. Bacterial resistance to FOS may be natural or acquired. Other properties of this drug include inhibition of bacterial adhesion to epithelial cells, exopolysaccharide biofilm penetration, immunomodulatory effect, phagocytosis promotion and protection against the nephrotoxicity caused by other drugs. FOS has chemical characteristics not typically observed in organic phosphoric compounds and its molecular weight is almost the lowest of all the antimicrobials. It tends to form salts easily due to its acidic nature (disodium salt, for intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration; calcium and trometamol salt: for oral (PO) administration). FOS has a very low protein binding (<0.5%) which, along with its low molecular weight and water solubility, contributes to its good diffusion into fluids (cerebrospinal fluid, aqueous and vitreous humor, interstitial fluid) and tissues (placenta, bone, muscle, liver, kidney and skin/fat). In all species, important differences in the bioavailability have been found after administration in relation to the various derivatives of FOS salts. Pharmacokinetic profiles have been described in humans, chickens, rabbits, cows, dogs, horses and weaning piglets. The low toxicity and potential efficacy of FOS are the main factors that contribute to its use in humans and animals. Thus, it has been used to treat a broad variety of bacterial infections in humans, such as localized peritonitis, brain abscesses, severe soft tissue infections, cystitis and other conditions. In veterinary medicine, FOS is used to treat infectious diseases of broiler chickens and pigs. In broilers, it is administered for the treatment of E. coli and Salmonella spp. infections. In piglets, the drug is prescribed to treat a wide variety of bacterial infections. FOS penetration is demonstrated in phagocytic, respiratory (HEP-2) and intestinal (IPEC-J2) cells. Although not widely used in animals, the drug has shown good results in human medicine. The potentialities of FOS suggest that this drug is a promising candidate for the treatment of infections in veterinary medicine. For these reasons, the aim of this work is to provide animal health practitioners with information on a drug that is not extensively recognized.

Integrons are one of the genetic elements involved in the acquisition of antibiotic resistance. The aim of the present research is to investigate the presence of integrons in commensal Escherichia coli (E. coli) strains, isolated from pigs at different stages of production system and from the environment in an Argentinian farm. Five sows postpartum and five randomly chosen piglets from each litter were sampled by rectal swabs. They were sampled again at day 21 and at day 70. Environmental samples from the farm were also obtained. E. coli containing any integron class or combination of both integrons was detected by polymerase chain reaction in 100% of sows and in piglets at different stages of production: farrowing pen stage 68.1%;, weaning 60%, and growing/finishing 85.8%, showing an increase along the production system. From environmental samples 78.4% of E. coli containing any integron class was detected. We conclude that animals and farm environment can act as reservoirs for potential spread of resistant bacteria by means of mobile genetic elements as integrons, which has a major impact on production of food animals and that can reach man through the food chain, constituting a problem for public health.

Fosfomycin (FOS) is an antibiotic used in pig farms for treatment and prevention of infections caused by resistant bacteria during the post-weaning period. Antibiotics and non-toxic concentrations of mycotoxins, such as deoxynivalenol (DON) are frequently found in the diet of animals. These compounds can establish interactions in the intestinal tract, which could affect and/or modify the penetration of FOS to enterocytes. The aim of this study was to determine the penetration of FOS into IPECJ-2 cells, a cell line derived from the small intestine of piglets, in the presence and absence of DON. The results from this study showed that there was statistically significant difference in the intracellular concentration of FOS between cells incubated with 580 µg/ml FOS and cells incubated with 580 µg/ml FOS and 1 µg/ml DON. The Cmax of the intracellular antibiotic in the culture plates incubated with FOS in absence of DON was 45.81 µg/ml with a tmax of 4 h. When IPEC-2 cells were incubated with FOS and DON the Cmax was 20.06 µg/ml and the tmax was 30 min. It is concluded that the non-toxic concentration of DON on IPEC-J2 cells after short-term exposure, interferes with the pharmacokinetics of the antibiotic.

Acetaminophen (APAP) administration results in hepatotoxicity and hematotoxicity in cats. The response to three different treatments against APAP poisoning was evaluated. Free glutathione (GSH) (200mg/kg), niosomal GSH (14 mg/kg) and free amino acids (180 mg/kg of N-acetylcysteine and 280 mg/kg of methionine) were administered to cats that were intoxicated with APAP (a single dose of 150 mg/kg, p.o.). Serum concentration of alanine aminotransferase (ALT) along with serum, liver and erythrocyte concentration of GSH and methemoglobin percentage were measured before and 4, 24 and 72 hours after APAP administration. Free GSH (200 mg/kg) and niosomal GSH (14 mg/kg) were effective in reducing hepatotoxicity and hematotoxicity in cats intoxicated with a dose of 150 mg/kg APAP. We conclude that both types of treatments can protect the liver and haemoglobin against oxidative stress in APAP intoxicated cats. Furthermore, our results showed that treatment with niosomal GSH represents an effective therapeutic approach for APAP poisoning.

Disodium-fosfomycin pharmacokinetics has been studied in different species after oral, intravenous, intramuscular and subcutaneous administration. At present there are neither documented clinical experiences of the use of fosfomycin in pigs nor any published studies in weaning piglets, although it is a period of high incidence of infectious diseases. The pharmacokinetics and the bioavailability of sodium fosfomycin were studied in post weaning piglets after intravenous and intramuscular administration of 15 mg/kg of body weight. Plasma concentrations were measured by a high-performance liquid ms/ms. After IV administration the area under the fosfomycin concentration:time curve in plasma was AUC(0-12) of 120.00 ± 23.12 μg h/ml and the volume of distribution (Vd) of 273.00 ± 40.70 ml/kg. The elimination was rapid with a plasma clearance of 131.50 ± 30.07 ml/kg/h and a T(1/2) of 1.54 ± 0.40 h. Peak serum concentration (Cmax), Tmax, AUC(0-12) and bioavailability for the IM administration were 43.00 ± 4.10 μg/ml, 0.75 ± 0.00 h, 99.00 ± 0.70 μg h/ml and 85.5 ± 9.90% respectively. Different authors have determined a minimum inhibitory concentration (MIC90) ranging from 0.25 μg/ml for Streptococcus sp. and 0.5 μg/ml for Escherichia coli. Considering the above, and according to the values of plasma concentration vs time profiles observed in this study, effective plasma concentrations of fosfomycin for sensitive bacteria can be obtained following IV and IM administration of 15 mg/kg in piglets., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Pharmacokinetic parameters were established for flurbiprofen (FBP) after intravenous (i.v.) administration (0.5 mg/kg) of niosomal and nonniosomal formulations in dairy cattle. Niosomes of FBP showed a drug loading of 92.0 +/- 0.7% and the intravenous administration of the FBP niosomes to dairy cattle did not produce any immunological reaction associated to niosomal components. Niosomal FBP was slowly eliminated from plasma and mean residual time (MRT) and AUC(0-->t) and t (1/2) values were significantly higher than those for non niosomal FBP formulations. The results presented in this study indicate that the long circulation of FBP niosomes offers a potential application for improving the pharmacokinetic parameters of short half-life drugs for clinical use. Niosomes offer new promising perspectives of drug delivery modules in bovine therapeutics.

Wheat (as bran) and corn (as dry grain or fermented feed) are main ingredients of feedstuffs used in local cattle and pig farms in the South of the Buenos Aires Province (Argentina). Therefore, determining mycobiota and mycotoxins in wheat and corn is of prime importance for developing feed management techniques to optimise animal production and to minimize toxicity. Then, a mycological survey was carried out in the Southeastern part of the Buenos Aires Province, in order to identify the mycobiota and the main mycotoxins present in fermented feed, wheat grain and corn grain samples. Samples were cultured for fungal quantification, isolation and identification, and analysed for deoxynivalenol (DON), zearalenone (ZEA), T-2 toxin and aflatoxins (AFLA). Penicillium (74%), Aspergillus (32%) and Scopulariopsis (21%) were the prevalent genera in fermented feed. Penicillium (70%), Fusarium (47%) and Aspergillus (34%) were the most frequent fungi isolated from corn. Penicillium (42%), Fusarium (27%) and Alternaria (25%) were the most frequently recovered genera from wheat. DON was detected in 59% of the corn samples, in 45% of the wheat samples and in 38% of the silage samples. ZEA was detected in 36% of the corn samples, in 49% of the wheat samples and in 16% of the silage samples. T-2 toxin and aflatoxin B1 were each detected in 4% of the corn samples. Eighteen percent of the fermented feed samples showed T-2 contamination. Fermented feed and wheat samples were negative for AFLA.

Glutathione is an important intracellular tripeptide with multiple functions. Abnormal glutathione metabolism is thought to play an important role in various diseases of cats. However, no data regarding concentration of plasma glutathione are available for domestic cats. This study discusses the development of a rapid, simple high pressure liquid chromatography method for measurement of reduced glutathione (GSH), oxidized glutathione (GSSH) and total glutathione (GSHt) in plasma, for the purpose of establishing baseline data for future studies. The mean concentrations of GSH, GSSH and GSHt were 4.51+/-1 microM; 19.44+/-3.79 microM (expressed as GSH equivalent) and 23.59+/-3.89 microM, respectively. This is the first report of plasma glutathione concentrations in this species.

Flurbirpofen (FBP), a member of the 2-aryl propionate nonsteroidal anti-inflammatory drug class, has potent anti-inflammatory and analgesic properties. The commercial preparation is a racemic mixture of the R(-) and S(+) enantiomers of FBP. In this study, R(-) and S(+) FBP were used to investigate the metabolic chiral inversion. Each enantiomer was administered separately (0.25 mg/kg) and in a racemic mixture (0.5 mg/kg) intravenously to horses. Plasma and synovial concentration of each enantiomer was determined and the disposition of each was analyzed. After intravenous administration of R(-) FBP and S(+) FBP to horses no chiral inversion was detected. After the administration of the FBP racemate and individual enantiomers no differences were observed between pharmacokinetic parameters [t(1/2beta) (h), Cl (L/h.kg), AUC (microg.h/mL), Vss (L/kg) and MRT (h)] for R(-) and S(+) FBF. Synovial fluid concentrations of both FBP enantiomers were lower than plasma concentrations and no stereoselective differences were detected. These data indicate that the disposition of FBF in horses is not enantioselective and demonstrate a difference in the pharmacokinetic behavior of the enantiomers as compared with other 2-aryl-propionic acids, such as carprofen, ketoprofen and vedaprofen in the horse.

Suprofen (SPF) is a non-steroidal anti-inflammatory drug (NSAID), which belongs to the 2-arylpropionic acids subclass. As a result of their chiral characteristics, these compounds have shown a marked enantioselective behaviour with a high degree of interspecies variation. They are mainly eliminated by glucuronidation. Plasma, biliary and urine disposition of SPF was investigated in the cat after intravenous administration of the racemate (dose 2 mg/kg). Both enantiomers exhibited similar disposition profiles in plasma with no evidence of chiral inversion. During bile sampling time, recovered acylglucuronides of R (-) and S (+) SPF were less than 1% of the total dose administered. Only free SPF was recovered in the urine, representing 0.12% of the administered racemic SPF dose. The results indicate that neither chiral inversion nor glucuronidation predominate in SPF disposition in cats., (Copyright Harcourt Publishers Ltd.)

The chirality of drugs, with particular reference to agents used in veterinary medicine, is reviewed. Basic concepts of chirality and aspects of the methodology for the separation of enantiomers are considered. Chiral compounds are in common use in animals and their pharmacological actions and side-effects (pharmacodynamics) and absorption into and fate within the body (pharmacokinetics) are of fundamental importance; pharmacodynamic and pharmacokinetic properties of enantiomeric pairs commonly differ and this has major implications for their effective and safe therapeutic use. As examples of the particular significance of chirality in veterinary medicine, the following drug classes are reviewed; benzimidazole anthelmintics, cloprostenol, verapamil, ketamine, halogenated hydrocarbon anaesthetics and 2-arylpropionic acid anti-inflammatory drugs. The implications of chirality for drug product development and approval by registration authorities are discussed.

The pharmacokinetics and bioavailability of cefoperazone (CPZ) were studied following intravenous (IV) and intramuscular (IM) administration of single doses (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples were measured following IV administration. CPZ concentrations in serum, synovial fluid and spongy bone samples were measured following IM administration. After IV administration a rapid distribution phase (t1/2 (alpha): 4.22 +/- 2.73 min) was followed by a slower elimination phase (t1/2(beta) 0.77 +/- 0.19 h). The apparent volume of distribution was 0.68 +/- 0.10 L/kg. Mean synovial fluid peak concentration was 5.76 +/- 0.74 microgram/mliter. After IM administration a bioavailability of 42.00 +/- 5.33% was obtained. Half-life of absorption was 2.51 +/- 0.72 min and t1/2(beta) was 1.52 +/- 0.15 h. The mean synovial fluid and spongy bone peak concentrations at 2 h after IM administration were 2.91 +/- 0.85 microgram/mliter and 5.56 +/- 0.70 microgram/mliter, respectively.

Serum concentrations of ticarcillin were measured serially over a period of 12h in a cross over trial involving 6 healthy adult ewes after intravenous and intramuscular (IM) administration of 40 mg ticarcillin per kg body weight. Probenecid (40 mg/kg) was also administered IM immediately before the IM administration of 40 mg/kg ticarcillin. Pharmacokinetic values after intravenous administration were: half-life of elimination (T 1/2 beta) = 0.90 +/- 0.09 h; volume of distribution at steady state (Vdss) = 456.8 +/- 106.6 ml/kg, total body clearance (CIB) = 614.5 +/- 81.2 ml/h/kg. Ticarcillin persisted in serum at greater than or equal to 1.5 micrograms/ml for 4 hours. Pharmacokinetic and bioavailability values after intramuscular administration were: half-life of absorption (T 1/2 ab) = 8.08 +/- 1.98 min; T 1/2 beta = 0.96 +/- 0.07 h. Peak serum concentration (Cmax) was 31.11 +/- 6.02 micrograms/ml at 0.50 h (Tmax), bioavailability (F) was 0.82 +/- 0.09. After ticarcillin was administered IM together with probenecid the T 1/2 ab was 33.9 +/- 13.7 min, the T 1/2 beta 2.66 +/- 0.65 h, Cmax = 44.87 +/- 5.58 at 1.33 +/- 0.44 h, and F = 1.25 +/- 0.23.