Use of probabilistic modeling within a physiologically based pharmacokinetic model to predict sulfamethazine residue withdrawal times in edible tissues in swine.
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The presence of antimicrobial agents in edible tissues of food-producing animals remains a major public health concern. Probabilistic modeling techniques incorporated into a physiologically based pharmacokinetic (PBPK) model were used to predict the amounts of sulfamethazine residues in edible tissues in swine. A PBPK model for sulfamethazine in swine was adapted to include an oral dosing route. The distributions for sensitive parameters were determined and were used in a Monte Carlo analysis to predict tissue residue times. Validation of the distributions was done by comparison of the results of a Monte Carlo analysis to those obtained with an external data set from the literature and an in vivo pilot study. The model was used to predict the upper limit of the 95% confidence interval of the 99th percentile of the population, as recommended by the U.S. Food and Drug Administration (FDA). The external data set was used to calculate the withdrawal time by using the tolerance limit algorithm designed by FDA. The withdrawal times obtained by both methods were compared to the labeled withdrawal time for the same dose. The Monte Carlo method predicted a withdrawal time of 21 days, based on the amounts of residues in the kidneys. The tolerance limit method applied to the time-limited data set predicted a withdrawal time of 12 days. The existing FDA label withdrawal time is 15 days. PBPK models can incorporate probabilistic modeling techniques that make them useful for prediction of tissue residue times. These models can be used to calculate the parameters required by FDA and explore those conditions where the established withdrawal time may not be sufficient. (+info)
Influence of mouth washing procedures on the removal of drug residues following inhalation of corticosteroids.
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Mouth washing after inhalation of corticosteroids is effective for prevention of local adverse effects such as hoarseness and oropharyngeal candidiasis. To establish an optimal procedure for such mouth washing, we investigated the removal rates of drug residues remaining on the oropharyngeal mucosa using various mouth washing methods following inhalation. A beclomethasone dipropionate metered dose inhaler (BDP-MDI) (100 microg) and a fluticasone propionate dry powder inhaler (FP-DPI) (100 microg) were used. The effects of different mouth washing methods were evaluated by quantification of drugs in the expectorated rinse solution using an HPLC method. The amounts of BDP recovered in the rinse after gargling and rinsing for 5 s each were 47.1+/-13.6 microg, while they were 42.9+/-9.4 microg after rinsing alone for 10 s and 38.7+/-9.2 microg after gargling alone for 10 s. Under the same conditions, FP amounts were 32.9+/-7.3 microg, 28.9+/-2.4 microg, and 27.1+/-7.9 microg, respectively. In a comparison of washing time, the amounts of BDP recovered were 49.8+/-9.7 microg after gargling and rinsing for 2 s each, 53.5+/-10.2 microg after those for 3 s each, and 47.1+/-13.6 microg after those for 5 s each, while the amounts of FP under the same conditions were 36.4+/-2.4 microg, 33.3+/-6.4 microg, and 32.9+/-7.4 microg, respectively. As for the effect of time lag before mouth washing, the amount of BDP recovered decreased by 65.7% with a lag time of 1 min and by 5.6% after 10 min, while that of FP decreased by 51.1% with a lag time of 1 min and by 7.7% after 10 min. Our results suggest that the amount of drugs removed by mouth washing is significantly associated with the time lag between inhalation and mouth washing. We concluded that immediate gargling and rinsing after inhalation is most useful for the removal of drugs following inhalation of corticosteroids. (+info)
Application of a solid-phase fluorescence immunoassay to determine oxytetracycline and tetracycline residues in tissue of olive flounder (Paralichthys olivaceus).
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Parallux, a solid-phase fluorescence immunoassay (SPFIA) developed for antibotics residue detection in milk, was applied for analysis of fish tissue. The recommended therapeutic doses of oxytetracycline (OTC, 100 g/ton water, withdrawal period 30 days) and tetracycline (TC, 150 g/ton water, withdrawal period 30 days) were treated to a group of 35 olive flounders (Paralichthys olivaceus) using dipping administration. Muscle was sampled before and after drug treatment 1st, 2nd, 3rd, 5th, 7th, and 14th day. The concentration of oxytetracycline in muscle, determined by SPFIA, was compared with that of internal standard (100 ppb as oxytetracycline). The S/C ratio of sample inhibition value to cutoff inhibition value was employed as an index to determine the muscle residue in olive flounder. To investigate the recovery rate, and standard solutions were added to muscle samples to give final concentrations in muscle of 0.1 and 0.5 microg/ml. The recovery rates of all spiked samples were >89% of the spiked value. OTC and TC were detected in muscle of fishes treated until the 3rd day of withdrawal period. The present study showed that the SPFIA can be easily adopted in predicting tissue residues for OTC and TC in farmed fishes. (+info)
Pharmacokinetics and milk penetration of ibafloxacin after intravenous administration to lactating goats.
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The pharmacokinetic behavior of ibafloxacin was studied after intravenous administration of a single dose of 15 mg/kg to 6 healthy lactating goats. Plasma concentrations of ibafloxacin were determined by high-performance liquid chromatography with fluorescence detection. The data for concentration versus time could best be described by a 2-compartment model. The mean plasma ibafloxacin clearance (and standard error) was 1.05 (0.10) L/h x kg. The mean steady-state volume of distribution was 1.65 (0.42) L/kg. The mean elimination half-life was 3.76 (0.30) h. Ibafloxacin penetration from the blood to the milk was poor. The ratio between the areas under the concentration-time curve of milk and plasma was 0.20 (0.01), indicating scant penetration of ibafloxacin into the milk. (+info)
Orally administered erythromycin in rainbow trout (Oncorhynchus mykiss): residues in edible tissues and withdrawal time.
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Aquaculture production has notably increased in the last decades, mainly thanks to intensive farming. Together with market globalization, this gives rise to the spreading of several fish diseases, thus increasing the demand for veterinary drugs for aquatic species. Nonetheless, very few chemicals are registered for use in aquaculture, and fish farmers are often forced to resort to off-label use of drugs authorized for other food-producing animal species. Rainbow trout is the major farmed fish species in Italy and the second one in Europe. Erythromycin is the antibiotic of choice against gram-positive cocci, the major concern for trout farming, but it is not yet registered for aquaculture use in most European countries. The aim of this study was to follow the depletion of erythromycin in rainbow trout (Oncorhynchus mykiss), after its administration at 100 mg kg(-1) trout body weight day(-1) for 21 days through medicated feed (water temperature, 11.5 degrees C). Erythromycin residues in fish muscle plus skin in natural proportion were determined by a validated liquid chromatography-electrospray ionization-tandem mass spectrometry method. Interpolation of our data, following European Agency for the Evaluation of Medicinal Products guidelines, gives a withdrawal time of 255 degrees C-days ( degrees C-day = water temperature x days), thus showing that the general value (500 degrees C-day) recommended by the Council Directive (EEC) no. 82/2001 for off-label drug use in aquaculture would be too conservative in this case, with excessive costs for the farmers. Our study provides preliminary data for a more prudent use of erythromycin in rainbow trout, suggesting a possible withdrawal time after treatment. (+info)
Multi-residue determination of non-steroidal anti-inflammatory drug residues in animal serum and plasma by HPLC and photo-diode array detection.
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The European Union regulated the use of non-steroidal anti-inflammatory drugs (NSAIDs) in animal production and set the official analytical controls to detect their residues in plasma, serum, and milk within the frame of national monitoring programs in each member state. In this work, a multi-residue reversed-phase high-performance liquid chromatography with diode array detector (DAD) method is described for the simultaneous determination of 13 NSAIDs in serum and plasma of farm animals. Chromatographic separation by a C12 stationary phase column with a linear gradient is able to resolve all the compounds considered: salicylic acid, ketoprofen, flurbiprofen, phenylbutazone and its metabolite (oxyphenbutazone), carprofen, ibuprofen, naproxen, niflumic acid, suxibutazone, diclofenac, mefenamic acid, and tolfenamic acid. These compounds are chosen as the most representative of the different NSAID chemical sub-classes. The DAD analysis allows the confirmation of all drugs on the basis of their own UV-vis spectrum, according to the requirements of the European Council Decision 2002/657/EC. Moreover, the method is in-house validated, evaluating mean recoveries, specificity, repeatability, and within-laboratory reproducibility as the performance parameters required by the Decision. The results of this study indicate the method is specific and repeatable, with the mean percentage recoveries of the drugs ranging between 72.5% and 104.5%. Only salicylic acid has poor recovery, with results ranging between 36.3% and 54.9%. (+info)
The effect of discontinued use of antimicrobial growth promoters on the risk of therapeutic antibiotic treatment in Danish farrow-to-finish pig farms.
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This study estimated the effect of discontinued use of antimicrobial growth promoters (duAGPs) on the risk of antibiotic treatment for diarrhoea, arthritis, pneumonia, unthriving and miscellaneous disorders in Danish pig farms. The estimation was done in a case-crossover study comparing: (1) the proportion of days per farm where treatment was performed (PDT) and (2) the proportion of pigs treated per day per farm at days where treatment was performed (PPT) before and after duAGPs at 68 farrow-to-finish farms. The farms were selected using a two-stage (veterinarian/farm) convenience sampling. On average, during the first year after duAGPs there was a significant increase in the risk of antibiotic treatment for diarrhoea (PDT: OR 2.5, 95% CI 1.7-3.8; PPT: OR 1.6, 95% CI 1.1-2.2). However, the effect varied among farms--some farms experienced substantial problems, while others experienced few problems after duAGPs. No effect was identified for the risk of treatment for other diseases. (+info)
Time-resolved fluoroimmunoassay for 19-nortestosterone residues in aquaculture tissues.
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A competitive time-resolved fluoroimmunoassay (TR-FIA) was developed for the determination of 19-nortestosterone (17beta-NT) residues in aquaculture tissues. The limit of detection (LOD) was determined to be 0.08 ng g-1 and the limit of quantification (LOQ) was less than 0.8 ng g-1. The results obtained by the TR-FIA and ELISA showed a good correlation. The established TR-FIA was validated for the determination of incurred aquaculture tissues and confirmed by liquid chromatography tandem mass spectrometry (LC/MS/MS). This proposed technique could be applied to routine residue analysis. (+info)