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J. HENRI C. BUREL P. SANDERS & M. LAURENTIE 《Journal of veterinary pharmacology and therapeutics》2009,32(5):451-456
The pharmacokinetics of monensin including apparent volume of distribution, total body clearance, systemic bioavailability, partition coefficients and tissue residues were determined in chickens. The drug was given by intravenous injection in the left wing vein at the dose of 0.46 mg/kg and by intracrop administration at the dose of 4 mg/kg according to a destructive sampling. The pharmacokinetic variables were compared after noncompartmental, naïve averaged, naïve pooled and nonlinear mixed-effects modelling analyses. Partition coefficients and tissue residues were determined after a treatment with feed additives (125 mg/kg of feed) of 33 days. The clearance, volume of distribution and bioavailabilty were approximately 2.2 L/h/kg, approximately 9 L/kg and approximately 30% respectively except with nonlinear mixed effects models that presented values of 1.77 L/h/kg, 14.05 L/kg and 11.36% respectively. Tissue/plasma partition coefficients were estimated to 0.83, 3.39 and 0.51 for liver, fat and thigh muscle respectively. Monensin residues after treatment were not detected 6 h after withdrawal except for fat where monensin was still quantifiable 12 h after. Pharmacokinetic variables seem to be inaccurate when assessed with non linear mixed-effects modelling associated to destructive sampling in chickens. Values varied slightly with noncompartmental, naïve averaged and naïve pooled analyses. The absorption, elimination and partition parameters will be incorporated into a physiologically based pharmacokinetic model and the depletion study will be used to test the ability of this model to describe monensin residues in edible tissues under different dosage regimens. 相似文献
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S. K. CHANG J. L. DAVIS C. N. CHENG R. H. SHIEN M. K. HSIEH B. W. KOH C. C. CHOU 《Journal of veterinary pharmacology and therapeutics》2010,33(5):471-479
Chang, S. K., Davis, J. L., Cheng, C. N., Shien, R. H., Hsieh, M. K., Koh, B. W., Chou, C. C. Pharmacokinetics and tissue depletion of florfenicol in Leghorn and Taiwan Native chickens. J. vet. Pharmacol. Therap. 33 , 471–479. Florfenicol (Ff) is a synthetic antibiotic with a broad antibacterial spectrum and high therapeutic effectiveness that was specifically developed for veterinary use. In the present study, tissue residual levels and the pharmacokinetics of Ff after oral administration of 30 mg/kg to Leghorn and Taiwan Native chicken were studied. Furthermore, differential pharmacokinetics between leg and breast muscles were compared using samples collected from an optimized microdialysis model designed for avian species. Significant differences in Cmax were detected between the plasma and muscle microdialysates, and between the breast and leg microdialysates of the Leghorn chickens by noncompartmental pharmacokinetic analysis. After a single oral dose of Ff at 30 mg/kg, the drug was quickly absorbed and widely distributed with tissue penetration factors significantly different between leg and breast muscles. The serum protein binding of Ff was estimated to be 16.8 ± 1.2%. Significant breed differences in tissue depletion were noted and characterized by higher Ff concentration in the brain, lung, kidney and at least 12 h longer resident times in kidney, heart and spleen for Taiwan Native chicken. Results from this investigation demonstrate the practicality of using in vivo microdialysis in chickens for pharmacokinetic studies and reveal significant time‐dependent differences in the free concentrations of Ff in leg and breast muscles. The tissue depletion study signified breed differences in tissue residue concentration and detection times between Leghorn and Taiwan Native chickens. Therefore, currently used withdrawal times for Ff in chickens can not be assumed safe for Taiwan Native chickens. 相似文献
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Lymphocytic depletion of bursa of Fabricius and thymus in chickens inoculated with Escherichia coli 总被引:2,自引:0,他引:2
Specific-pathogen-free 10-week-old chickens were inoculated via the air sac with Escherichia coli and showed lymphocytic depletion of bursa of Fabricius and thymus. In experiment I, chickens were necropsied at 12 and 24 hours, 2, 3, and 5 days after inoculation. At 12 hours after inoculation there was lymphocytic depletion in the medulla of lymphoid follicles of the bursa. At 24 hours after inoculation there was lymphocytic depletion also in the cortex of follicles and edema in interfollicular interstitium and follicular medulla. At 2 and 3 days after inoculation there were more marked lymphocytic depletion in medulla and cortex, and fibrosis in interfollicular interstitium. Partial repopulation of follicles with lymphocytes was seen at 5 days after inoculation. In the thymus, lymphocytic depletion occurred in the cortex. At 12 hours after inoculation, lymphocytic necrosis increased in number more than that of control chickens. The width of the cortex and medulla decreased. At 24 hours after inoculation, lymphocytic necrosis increased further. At 2 to 5 days after inoculation, the boundary between the cortex and medulla of lobules was obscure and cellular elements of the cortex and medulla were mingled. In experiment II, chickens were necropsied as in experiment I and also at 8 and 14 days after inoculation. The relative weights of the bursa and thymus reduced rapidly to minimal relative weights at 8 days after inoculation. At 14 days after inoculation, both bursa and thymus had normal relative weights and histological structures. These findings indicate that E. coli infection may induce transient lymphocytic depletion of lymphoid tissues in the chicken. 相似文献
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R F Slocombe J Malark R Ingersoll F J Derksen N E Robinson 《American journal of veterinary research》1986,47(10):2313-2317
Twenty-six Holstein calves were treated with hydroxyurea in order to induce neutropenia. Calves were given a daily dosage of hydroxyurea (70 mg/kg of body weight) for 4 consecutive days, and clinical signs, blood leukograms, hemograms, and platelet counts were monitored daily until the calves became neutropenic. Once a neutropenic state was induced, the calves were anesthetized and pulmonary function tests were performed. Subsequently, calves were euthanatized and complete necropsies were performed. Hydroxyurea treatment induced profound neutropenia in all calves by 8 days after initiating treatment, with mild decreases in circulating numbers of lymphocytes. Treatment did not cause clinical or pulmonary functional abnormalities. Severe pathologic changes were restricted to the bone marrow and consisted of partial to complete destruction of myeloid elements, with less severe effects on erythrocytic precursors and megakaryocytes. Hydroxyurea was useful for the induction of neutropenic states in calves and did not induce major toxic effects on other cells when given at 70 mg/kg. 相似文献
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Musser JM Anderson KL Boison JO 《Journal of the American Veterinary Medical Association》2001,219(3):346-350
OBJECTIVE: To determine tissue depletion of penicillin G in calves after oral ingestion with milk replacer and estimate a withdrawal period. DESIGN: Longitudinal controlled trial. ANIMALS: 26 Holstein calves. PROCEDURE: Once daily, 24 calves were fed milk replacer containing procaine penicillin G (0.68 mg/kg [0.31 mg/lb] of body weight); 2 calves served as controls. After 1 feeding, 12 calves were euthanatized in groups of 3 each 4, 6.5, 9.5, and 13 hours after feeding. After 14 days, 12 calves were euthanatized in groups of 3 each 4, 6.5, 9.5, and 13 hours after the final feeding. Concentrations of penicillin G were determined in tissues, blood, and urine by use of high-performance liquid chromatography. RESULTS: Penicillin G was not detected in muscle samples of treated calves. The highest concentrations of penicillin G in plasma, kidney, and liver were 13 ng/ml, 92 ng/g, and 142 ng/g, respectively. Thirteen carcasses had violative drug residues; 12 had violative residues in the liver only, and 1 had violative residues in the liver and kidney. A 21-hour withdrawal period was estimated. CONCLUSIONS AND CLINICAL RELEVANCE: Liver had the highest concentration of penicillin G and was most likely to have violative residues. Feeding calves milk containing penicillin G has the potential to cause violative drug residues in tissues. It is recommended to observe an appropriate withdrawal time prior to slaughter if calves are fed milk from cows treated with penicillin G. 相似文献
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J F Nouws T B Vree M Baakman F Driessens H J Breukink D Mevius 《American journal of veterinary research》1986,47(3):642-649
Plasma disposition, protein binding, urinary recovery, and renal clearance of sulfamethazine (SMZ), its N4-acetylsulfamethazine (N4-SMZ), and its 2 hydroxy metabolites--6-hydroxymethylsulfamethazine (SCH2OH) and 5-hydroxysulfamethazine (SOL)--and the glucuronide of the latter were studied in 7 cows and 7 calves to determine the relationship between these values and the age of the animal and dosage applied. A capacity-limited hydroxylation of SMZ into SCH2OH was observed in cows and calves given dosages of 100 to 200 mg/kg. A biphasic SMZ elimination curve and steady state in SCH2OH plasma concentration (6 to 15 micrograms/ml) were observed. The N4-SMZ plasma concentration-time curve was parallel to that of SMZ at the dosages and in all animals. The total body clearance and the cumulative urinary recovery (expressed as percentage of the dose) for SMZ and its metabolites depended on drug dosage and age of the animals. At dosages of SMZ less than 25 mg/kg, the main metabolite in the urine of calves and cows was SCH2OH (23% to 55.2%), whereas in calves given a larger dosage (100 mg/kg), the N4-SMZ and SOH percentages increased. The plasma protein binding of SMZ and its metabolites depended on the SMZ plasma concentration. Hydroxylation lowered the protein binding (from 75-80%) to 50%. The renal clearance of SMZ was dependent on urine flow in all animals. The renal clearance of the SCH2OH metabolite was 2 to 3 times greater than the creatinine clearance value; thus, this compound was excreted by glomerular filtration and partly by tubular secretion.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Plasma pharmacokinetics and tissue depletion of cyromazine and its metabolite melamine following oral administration in laying chickens
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T. Rairat S. C. Ou S. K. Chang K. P. Li T. W. Vickroy C. C. Chou 《Journal of veterinary pharmacology and therapeutics》2017,40(5):459-467
The study was designed to characterize the plasma pharmacokinetics and tissue depletion profiles (including eggs) of cyromazine (CYR) in chickens following oral administration alone or in combination with melamine (MEL). In order to assess the pharmacokinetic profile of CYR, chickens were administered 1 or 10 mg/kg (single oral doses), whereas residue studies were conducted in chickens fed CYR alone (5 or 10 mg/kg) or CYR (5 mg/kg) and MEL (5 mg/kg) for a period of 14 days. Estimates for the apparent volume of distribution (1.66 L/kg), clearance (7.17 mL/kg/min), and elimination half‐life (2.82 h) were derived by noncompartmental analyses. The highest concentration of CYR occurred in liver but fell below detectable limits within 3 days following drug withdrawal from feed. Combined feeding of MEL with CYR did not significantly alter CYR tissue levels. CYR residues were detected only in egg white and were undetectable at the 2nd day postadministration. No MEL was found in eggs unless it had been added to the feed, and when present, it almost exclusively restricted to the egg white. Based upon the results of this initial study of CYR pharmacokinetics and residue depletion, it appears that use of CYR as a feed additive either alone (5 or 10 mg/kg) or in combination with MEL (both agents at 5 mg/kg) does not produce unsafe residue levels in edible products as long as appropriate withdrawal periods are followed for tissues (3 days) and eggs (2 days). However, our results indicate that adoption of a zero‐day withdrawal period should be reconsidered in light of these results. 相似文献
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J F Nouws D Mevius T B Vree M Baakman M Degen 《American journal of veterinary research》1988,49(7):1059-1065
The effect of molecular structure on the drug disposition and protein binding in plasma and milk, the urinary recovery, and the renal clearance of sulfadiazine, sulfamerazine, and sulfamethazine and of their N4-acetyl and hydroxy derivatives were studied in calves and cows. Sulfadiazine was highly acetylated and was slightly hydroxylated. Sulfamerazine and sulfamethazine were hydroxylated predominantly at the methyl group of the pyrimidine side chain; hydroxylation of the pyrimidine ring itself was more extensive for sulfamethazine than for sulfamerazine. At dosages between 100 and 200 mg/kg of body weight, sulfamethazine had a capacity-limited elimination pattern, which was not observed for sulfadiazine or sulfamerazine. The concentrations of the parent sulfonamide and its metabolites in plasma and milk were parallel, the latter being lower. Metabolite concentrations in milk were at least 8 times lower than those of the parent drug. Metabolism speeds drug elimination, producing compounds with renal clearance values higher than those of the parent drug. The effect on the metabolism and renal clearance of methyl substitution in the pyrimidine side chain is discussed. 相似文献
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用对-二甲氨基苯甲醛作显色剂,采用分光光度法测定饲料中磺胺二甲基嘧啶,最小检测量为0.05mg/kg,平均回收率分别为99.2%,变异系数≤5%,且该方法具有操作简便、快速,试剂消耗少,结果准确、离散程度小等优点。 相似文献
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R. C. WILSON L. S. HAMMOND C. H. CLARK W. R. RAVIS 《Journal of veterinary pharmacology and therapeutics》1989,12(1):99-102
Sulfamethazine has been used in therapy of equine disease for over 40 years (Welsh et al , 1946). Although sulfamethazine appears to be well absorbed when fed mixed with grain and is reported to reach its peak concentration 8 h after administration, its oral bioavailability and pharmacokinetics have not been reported (Schroeder et al. , 1948; Meier et al , 1980). The purpose of the present study was to determine the major pharmacokinetic values and the oral bioavailability of sulfamethazine at a dosage predicted to produce therapeutic blood concentrations in the pony. 相似文献
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磺胺二甲嘧啶在黑鲪体内的药物代谢动力学和残留消除研究 总被引:3,自引:0,他引:3
在(14±1)℃水温条件下,对黑鲪单次口灌100 mg/kg体重的磺胺二甲嘧啶,进行药物代谢动力学研究。在(20±2)℃水温条件下,按照《中华人民共和国水产行业标准磺胺类药物水产养殖使用规范》推荐剂量对黑鮶连续5天口灌给予磺胺二甲嘧啶,研究其在黑鮶体内的残留消除规律。血浆、肌肉和肝脏样品采用高效液相色谱检测,DAS2.0药物代谢动力学软件对数据进行处理分析。结果表明磺胺二甲嘧啶在黑鲪血浆、肌肉和肝脏中均符合一室模型,肝脏、血液和肌肉中药物达峰时间分别为6 h,8 h和10 h;峰值浓度分别为26.45μg/g、25.57μg/g和31.15μg/g;连续多次给药后,黑鮶血液、肌肉、肝脏中药物浓度分别在给药后12d、14d、15d后小于最大残留限量要求(0.1mg/kg)。 相似文献
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R. P. HUNTER S. ANTHONY BROWN † J. K. ROLLINS D. F. NELLIGAN 《Journal of veterinary pharmacology and therapeutics》1991,14(3):276-292
The effects of a bovine bronchopneumonia model on the pharmacokinetics and tissue residue depletion profiles of gentamicin in calves weighing 90-140 kg was explored. Two groups of heifer calves were used. The first was a normal group, while the second group had bronchopneumonia induced. A scoring system was developed to evaluate the extent of disease in the groups. A bimodal distribution of the serum pharmacokinetic parameters in the pneumonic group was caused by the effects of dehydration. When the severely dehydrated calves were omitted from the analysis, serum clearance of gentamicin was significantly higher in the pneumonic group than in the normal group (P less than 0.05). The pharmacokinetic equations used to fit the tissue concentrations varied from tissue to tissue and between groups. Because the best equation of a particular tissue's concentrations varied between groups, withdrawal periods, which are normally determined in healthy animals, may be inappropriate in diseased animals. Addition of several parameters (serum creatinine, serum urea nitrogen, albumin, fibrinogen, and total protein concentrations, white blood cell counts, central fluid volume, volume of distribution at steady state, area under the serum concentration vs time curve, serum clearance, and elimination rate constant) to these tissue-depletion models using multiple regression improved the prediction of a concentration in a given tissue. 相似文献
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本研究以磺胺二甲嘧啶的单克隆抗体为核心试剂建立ELISA检测方法,可检测鸡饲料和猪饲料中的磺胺二甲嘧啶。ELISA方法的标准曲线为:y=-29.448x 74.565,R2=0.9917,IC50=6.8ng/mL,线性范围为0.7~71.3ng/mL,检测限为0.3ng/mL。选择磷酸盐缓冲溶液(0.01mol/L,pH7.4)为提取溶剂,以0.1、1μg/g和10μg/g的浓度添加于空白的鸡和猪配合饲料时,其回收率为73.3~107.3%,变异系数为0.9%~19.2%。 相似文献
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磺胺二甲嘧啶残留检测方法的研究进展 总被引:6,自引:0,他引:6
磺胺二甲嘧啶已广泛应用于家畜传染病和球虫病的治疗和预防,但该药物在肉类食品中的残留量日益受到人们的重视。本文就磺胺二甲嘧啶残留的常用检测方法作一综述。 相似文献