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1.
为了预测肉鸡连续肌内注射氟苯尼考后各组织中药物的残留浓度,利用文献检索获得的肉鸡生理学和解剖学参数及氟苯尼考在各组织中的组织-血浆分配系数,建立了一个包含13个模块的血流限速型生理药动学模型。模型中包含了氟苯尼考自注射部位的吸收、从肾脏的排泄、在肝脏的代谢及肝肠循环模块。研究利用该模型成功预测了肉鸡连续5次肌内注射氟苯尼考(30 mg/kg·d)后各组织中氟苯尼考的残留浓度。结果表明:多次肌内注射后,氟苯尼考在肉鸡体内吸收迅速、分布广泛、消除缓慢,且在注射部位浓度最高,消除最慢。  相似文献   

2.
此研究通过采用养殖场饲料配方喂养猪,在不同时间通过反相高效液相色谱法测定三聚氰胺在猪的背肌、腿肌、肝脏、肺、肾脏、心脏、血尿中的残留量,用以研究三聚氰胺在猪体内的残留特征和代谢规律。结果表目月.三聚氰胺在猪体内为惰性代谢,大部分以原型从尿液排出,大剂量应用时主要对肾脏产生毒性,同时对心脏等肾脏以外的器官也产生毒性作用。三聚氰胺在猪体内消除缓慢,残留期较长,基本残存时间在15d左右。  相似文献   

3.
本研究旨在分析土拉霉素在猪体内的残留消除规律并为制定休药期提供依据。采用猪颈部一次性肌内注射土拉霉素注射液,注射剂量为2.5mg.kg-1体质量,分别在给药后第0.5,5,12,18,25,36,48天,各宰杀5头取样。样品经乙腈提取,正己烷脱脂,C18固相萃取柱(SPE)净化后用高效液相色谱—串联质谱仪分析。结果显示,给药后第0.5天注射部位药物浓度最高,第36天所有组织的药物浓度均低于最高残留限量(MRL)。用WinNonlin软件分析各组织中的消除动力学参数,消除快慢依次为注射部位,肝脏,皮脂,肌肉,肺脏和肾脏,其消除半衰期(t1/2β)分别为117.06,193.14,197.60,207.64,228.99和232.61h。肺脏的药时曲线下面积(AUC)为1 220.59μg.h.g-1仅次于注射部位及肾脏,显著高于肌肉,肝脏及皮脂。由于肾脏为代谢器官,因此可确定肺脏为土拉霉素作用的靶部位。根据欧美等国家对土拉霉素制定的最高残留限量,计算得注射部位的休药期最长,为33d。结果提示土拉霉素注射液吸收迅速,体内分布广,作用时间长。建议休药期为33d。  相似文献   

4.
为研究自制盐酸多西环素注射液在猪体内的残留消除规律,以10 mg/kg剂量给健康猪肌内注射盐酸多西环素注射液,每日1次给药,连续三次。在最后一次给药后7、14、21、28和35 d时间点采集肌肉、肝脏、肾脏、脂肪和注射部位肌肉,用UPLC-MS/MS法测定组织中多西环素残留量。结果表明,给药35 d后,肌肉、肝脏、肾脏、脂肪和注射部位肌肉中的多西环素残留量分别为18、24、69、10、59μg/kg,均低于最高残留限量。用WT1.4软件计算休药期,盐酸多西环素注射液在猪肌肉、肝脏、肾脏、脂肪和注射部位肌肉中的休药期分别为33.9、23.8、24.8、0和36.9 d,为保证兽药安全使用、消费者身体健康与食品安全,建议盐酸多西环素注射液在猪的休药期为42 d。  相似文献   

5.
为预测肉鸡多次灌胃氟苯尼考后各可食性组织中的残留药物浓度,研究利用文献检索获得的肉鸡生理学和解剖学参数,建立了一个包含11个组织在内的血流限速型生理药动学(PBPK)模型,模型中包含了氟苯尼考的口服给药、胃肠道吸收、肾脏排泄、肝脏代谢及肝肠循环模块,该PBPK模型成功预测了肉鸡连续5d灌胃氟苯尼考(30mg/kg·d)后各组织中的药物浓度。结果表明,多次灌胃给药后,氟苯尼考在肉鸡体内吸收迅速、分布广泛、消除缓慢,其中在肾脏中分布最多,而在胆汁中消除最慢。  相似文献   

6.
通过喹赛多(Cyadox,CYX)在大鼠体内消除规律研究,了解其对食品安全的影响,并为今后的药理学和毒理学研究提供较为详细的数据基础,研究建立了喹赛多及其两种主要代谢产物脱二氧喹赛多(BDCYX)和喹噁啉-2-羧酸(QCA)的提取和HPLC检测方法,并以大鼠作为研究载体,按推荐剂量连续混饲给药7 d后,研究喹赛多及其两种代谢物在血浆、肌肉、肝脏中消除规律;一次性灌胃给药后研究喹赛多及其两种代谢物在排泄物中的消除规律特点。结果表明,CYX和BDCYX在0~24 h和24~48 h时间段的粪便中可大量检出,在血浆、肌肉、肝脏和尿液中未检出;QCA在6 h的肌肉中有少量残留,在肝脏中一直到72 h还有一定量的残留,在血浆和粪便中未发现其存在。本研究结果为今后喹赛多在体内处置研究提供了可直接借鉴的技术手段和理论基础。  相似文献   

7.
牛皮下单次注射爱普菌素注射剂,剂量为0.5 mg/kg,给药后在不同时间点采取肌肉、肝脏、肾脏和脂肪等组织样品检测爱普菌素残留,采用3P97软件对组织残留-停药时间数据进行分析.结果表明,注射部位、肝脏中爱普菌素残留浓度变化符合二室开放模型,肌肉、肾脏、脂肪中EPR残留浓度变化符合一室开放模型.爱普菌素经皮下注射后Tmax均小于1 d(0.17~0.76 d),Cmax范围在37.32~1453.79 ng/g之间.MRT范围在7.54~14.79 d之间,与T1/2el范围2.91~19.50 d相一致,说明药物在动物体内消除缓慢.  相似文献   

8.
为了预测氟苯尼考在肉鸡体内的残留休药期,在前期建立的生理药动学模型基础之上,加入了氟苯尼考胺生成及处置模块,并与蒙特卡洛模拟相结合预测得到了肉鸡连续5次灌胃氟苯尼考(25 mg/kg·d)后各组织中氟苯尼考胺的浓度,最终以氟苯尼考胺为残留标示物计算得到氟苯尼考在肉鸡体内的残留休药期为1 d,并且多次灌胃给药后,氟苯尼考胺在肉鸡肝脏和肾脏中残留浓度较高,在皮脂中残留浓度较低,但自皮脂中消除最慢,且存在一定蓄积效应。  相似文献   

9.
恩诺沙星注射液在猪体内的残留消除研究   总被引:1,自引:0,他引:1  
为研究恩诺沙星在猪体内的残留消除规律,验证休药期,以2.5 mg/kg体重肌内注射10%恩诺沙星注射液,每日2次,连续3 d。在最后一次给药后0、3、5、7、10 d时间点,采集肌肉、肝脏、肾脏、脂肪和注射部位肌肉,HPLC法测定组织中的恩诺沙星及其代谢物环丙沙星的残留量,并用WT1.4软件计算休药期。结果显示,恩诺沙星在猪肌肉、肝脏、肾脏、脂肪和注射部位肌肉的休药期分别是5.6、13.4、8.2、3.0、5.5 d。为保证兽药使用安全、消费者健康和食品安全,推荐恩诺沙星注射液在猪的休药期为14 d。  相似文献   

10.
本文建立了检测环丙沙星在肉鸡组织中残留的高效液相色谱分析法。并利用建立的方法对环丙沙星在肉鸡体内的残留和消除规律进行了研究。每1L水中添加200mg环丙沙星,对120只肉鸡连续给药5d,使用高效液相色谱法对肌肉、肝脏和肾脏进行药物残留分析。残留结果研究表明,至体药13d时,在肝脏和肾脏中仍可检出0.015mg/kg和0.008mg/kg环丙沙星。在本试验条件下,建议环丙沙星,临床体药期为15d左右。  相似文献   

11.
Gentamicin was administered IM to 6 healthy, mature, lactating cows at a dosage of 3.5 or 5 mg/kg of body weight every 8 hours for 10 consecutive days (total, 30 doses). Endometrial biopsies were done at 72, 136 or 144, and 216 hours after the first dose was administered. On the 10th day, just before the last dose of gentamicin was administered, blood samples (designated 10th-day base-line samples) were obtained, and serial blood samples were obtained for 144 hours after the last injection was given. The cows were catheterized on the 10th day, and urine was obtained for 10 to 18 consecutive hours. Milk samples were also obtained. The cows were slaughtered at different times after the last dose was given, and samples were taken from 22 tissues and organs. Serum, milk, urine, and tissue gentamicin concentrations were determined by radioimmunoassay. Serum gentamicin concentrations were best fitted to a 2-compartment open model. The mean half-lives for absorption, distribution, and elimination were 0.16 +/- 0.14, 2.59 +/- 0.53, and 44.91 +/- 9.38 hours, respectively. Total body clearance and renal clearance were 1.65 +/- 0.69 and 1.32 +/- 0.25 ml/min/kg, respectively. The percentage of the dose excreted unchanged in the urine at 8 hours after the last dose was given was 98 +/- 15. As expected, of the tissues examined, the gentamicin concentrations in the kidney cortex and medulla were 1,500 times greater than those in serum. Renal function remained within the baseline range during the 10 days of gentamicin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

12.
Pharmacokinetics and urinary excretion of sulphadimidine in sheep and goats   总被引:1,自引:0,他引:1  
Pharmacokinetics and urinary excretion of sulphadimidine were determined in sheep and goats following a single intravenous injection (100 mg/kg). The disposition of the drug was described in terms of exponential expression: C p= Be -βt. Based on total (free and bound) sulphonamide level in plasma, pseudo-distribution equilibrium was rapidly attained and the half-life for elimination was 3.88 ± 0.64 h and 4.00 ± 0.34 h in sheep and goats, respectively. Body clearance, which is the sum of all clearance processes was 88 ± 19 and 55 ± 4 ml/kg/h in sheep and goats. Based on this study a satisfactory intravenous dosage regimen might consist of 100 and 60 mg sulphadimidine/kg body wt for sheep and goats and should be repeated at 12 h intervals. The influence of disease conditions on predicted plasma levels remain to be verified experimentally. Three-quarters of an intravenously injected dose of sulphadimidine was excreted in the urine of sheep and goats within 24 h of administration. The drug was mainly excreted as free amine while acetylated drug constituted 7 and 8% of total drug content in the urine of sheep and goats, respectively.  相似文献   

13.
The effects of different doses and dosage regimens on gentamicin pharmacokinetics and tissue residues were determined. Five groups of 12 sheep each were given gentamicin IM: group I, 2 mg of gentamicin sulfate/kg once; group II, 6 mg/kg once; group III, 18 mg/kg once; group IV, 6 mg/kg every 24 hours for 3 doses; and group V, 2 mg/kg every 8 hours for 9 doses. Serum concentrations were determined serially until sheep were killed and necropsied. Three sheep from each group were killed at 1, 4, 8, and 12 days after the last dose was administered. Renal cortex, renal medulla, liver, spleen, lung, skeletal muscle, and skeletal muscle at the injection site were assayed for gentamicin. An exponential equation was fitted to the serum concentrations, and various pharmacokinetic variables were determined. Serum clearance tended to increase as the single dose increased (P = 0.0588). Steady-state volume of distribution increased as the single dose was increased (P less than 0.05). Renal cortex contained the highest concentration of gentamicin which decreased in a biexponential manner. Concentrations in all tissues, except the injection site, were dependent upon the amount of the total dose, not the size of the injected dose (P less than 0.05). Concentrations at the injection site were up to 29 micrograms/g of tissue at 1 day after the last dose was given and were dependent upon the amount of total dose from multiple injections, not on the amount of each injected dose (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

14.
The excretion of Se75 via the feces and urine was studied in 30 sheep. Se75-sodium selenite was injected subcutaneously, using three different doses ranging from a tracer dose to a therapeutic dose. By the intraruminal route the substance was given in a tracer dose and a therapeutic dose. Se75-selenomethionine was injected subcutaneously and intraruminally in a tracer dose. Se75-selenocystine was given intravenously in a dose higher than that regarded as a therapeutic dose.After intraruminal injection a higher percentage of the dose was excreted via the feces than via the urine. After the two highest subcutaneous doses the urinary excretion was significantly higher than the fecal excretion. After a high selenium dose the percentage eliminated via the urine was greater than after a low dose, whether the subcutaneous or the intraruminal route was used.The fecal and urinary excretion of Se75 was of approximately the same order after injection of Se75-selenomethionine and Se75-selenocystine as after injection of the tracer dose of Se75-sodium selenite.In 2 sheep, 1.4 per cent and 3.7 per cent, respectively, of a therapeutic dose were excreted via the bile in 48 hours.Less than 3 per cent of a subcutaneous dose was eliminated with the expired air in 24 hours.Exactly how much of a therapeutic dose is excreted within, for instance, 2 weeks is difficult to establish, as the treated animal’s selenium supply with the feed is not known. In the experiments reported here, however, approximately 64 per cent of a subcutaneous and 75 per cent of an intraruminal therapeutic dose were excreted over a two-week period.  相似文献   

15.
Healthy mature cows (n = 6) were injected intrauterinally (IU) with gentamicin (50 ml of a 5% injectable solution) daily for 3 consecutive days. Venous blood and milk samples were collected at postinjection (initial) hours (PIH) 1, 3, 6, 9, 12, 24, 28, 31, 34, 37, 48, 51, 54, 57, 60, and 71, and endometrial biopsies were performed at PIH 6, 25, 48, 73, 95, and 119. Skeletal muscle biopsy samples were taken at PIH 25 and 73, and urine was collected every 1 or 2 hours during 12 consecutive hours after the first IU injection. Serum, milk, urine, and tissue concentrations of gentamicin were measured by radioimmunoassay. The highest mean serum concentration of gentamicin occurred during the 3 hours after each injection (2.49 +/- 1.46, 6.60 +/- 5.47, and 4.98 +/- 2.70 micrograms/ml). The mean peak concentration of gentamicin in milk occurred 3 to 6 hours after each injection. Mean peak urine concentration of gentamicin (256.8 +/- 127.9 micrograms/ml) was measured at PIH 6. The mean percentage of the first dose of gentamicin excreted in the urine within 12 hours was 14.78 +/- 3.56. The highest concentration of gentamicin in endometrial tissue (639.16 +/- 307.22 micrograms/g) was measured at PIH 6, decreasing to 9.64 +/- 3.55 micrograms/g before the next IU dose. Gentamicin was still detectable in endometrial tissue (0.86 +/- 0.43 microgram/g) 71 hours after the 3rd (last) IU injection.  相似文献   

16.
A radioimmunoassay (RIA) method for hexoestrol using an antiserum against hexoestrol-carboxypropyl ether-BSA and H3-hexoestrol was used to measure the concentrations of residues of hexoestrol in 0.1 ml biological fluids and 1 g edible tissues of implanted cattle and sheep. A preliminary ether extraction of biological fluids was necessary before RIA. The ether extract from tissues was further purified by solvent partition and silica gel column chromatography before RIA. Conjugates of hexoestrol were measured after enzymatic hydrolysis to free hexoestrol. In untreated animals residues were either not detected or very low in all tissues except urine from sheep. The method has a lower limit of detection of approximately 0–10 pg/ml for biological fluids in cattle and 20–100 pg/g for tissues in both sheep and cattle but the lower limit of detection in sheep urine was 70–294 pg/ml urine. In two heifers implanted with 60 mg hexoestrol and slaughtered 2 and 7 days after implantation, residues of hexoestrol were detected in all tissues except muscle with highest concentrations between 2 - 17 ng/g in urine, bile and kidney. The concentration of residues in steers which had been implanted with 45 mg or 60 mg hexoestrol and slaughtered at 90 days after implantation were 0, < 50, 46–96 and 200 pg/ml or g of plasma, muscle, liver and urine, respectively. The concentrations of hexoestrol in sheep implanted with 15 ml hexoestrol and slaughtered after 60 days were 70, 0, 964, 3100 and 4074 pg/g or ml of muscle, fat, liver, kidney and urine, respectively. No hexoestrol was found in control untreated cattle and sheep. It was concluded that some residues of hexoestrol were present in the excretory fluids and tissues of cattle and sheep which had been implanted with hexoestrol at the recommended dose and slaughtered after the recommended withdrawal periods. However, the concentrations of hexoestrol in muscle and fat were extremely low or not detectable. The method could be used for the routine screening of animals for treatment with hexoestrol.  相似文献   

17.
The second part of an experiment is described in which 20 one year old bulls were injected with diethylstilbestrol (DES) dipropionate containing preparations. Analysis of DES content was performed in several tissues, such as the injection site, diaphragm muscle, psoas muscle, liver, kidney and bile. In the injection site appreciable amounts of DES were found. Measurable amounts of DES were also found in liver and kidney until 4 weeks after injection. In bile, DES concentrations were even higher than those in urine, and were well correlated with DES concentrations in urine. Implications for screening purposes are discussed.  相似文献   

18.
旨在确定盐酸多西环素片按照给药说明给药后在羔羊体内的残留消除规律及休药期。将盐酸多西环素片根据体重以5 mg·kg-1内服给药,间隔24 h,连续给药5次。在最后1次给药后,分别在第0(12小时)、1、2、3、5、7和9天时间点采集羔羊脂肪、肌肉、肝和肾,采用建立并验证的HPLC-VWD方法测定组织中多西环素的含量。结果显示:方法学考察结果表明,在50~5 000 ng·mL-1添加的线性方程和相关系数为y=0.044x-0.414,R2=0.999。试验结果表明,多西环素在羔羊组织中代谢快速,最后1次给药后第9天,在肌肉、肝、肾和脂肪中均未检测到多西环素。本试验以5 mg·kg-1体重内服给予羔羊盐酸多西环素片后,根据欧洲药品评估机构法规《EMEA/CVMP/036/95》,建议盐酸多西环素片在羔羊组织中的休药期为2 d。  相似文献   

19.
Summary

The second part of an experiment is described in which 20 one year old bulls were injected with diethylstilbestrol (DES) dipropionate containing preparations. Analysis of DES content was performed in several tissues, such as the injection site, diaphragm muscle, psoas muscle, liver, kidney and bile. In the injection site appreciable amounts of DES were found. Measurable amounts of DES were also found in liver and kidney until 4 weeks after injection. In bile, DES concentrations were even higher than those in urine, and were well correlated with DES concentrations in urine.

Implications for screening purposes are discussed.  相似文献   

20.
Radiocarbon-labeled estra-1,3,5(10)-triene-3,17 beta-diol [4-14C-estradiol-17 beta; beta-estradiol] was suspended in commercial peanut oil and administered to each of three Holstein steer calves (142 to 170 kg body weight) by deep injection into neck muscle via 2.0 ml peanut oil carrier. The dosages were equivalent to .27 to .29 mg beta-estradiol/kg body weight. After dosing, radiocarbon was rapidly and almost totally eliminated in urine and feces. Most of the administered radiocarbon had been eliminated after 2 d, and by 11 d after treatment no radiocarbon was detectable in urine or feces of any calf. Of the total dose, 42.1 +/- 3.8% was excreted in urine and 57.7 +/- 5.2% was eliminated in feces. Analysis of noninjection site tissue samples (blood, brain, fat, kidney, liver and muscle) collected at sacrifice 14 d after treatment showed that none contained detectable radiocarbon residues, with the sensitivity limit for most tissues being 6 ppb beta-estradiol equivalent. Certain sections of muscle taken from the injection site area did contain detectable radiocarbon residues (as much as 69 ppb beta-estradiol equivalent), but total injection site area residues in each calf comprised less than .07% of the total administered dose. Radiocarbon in urine consisted primarily of alpha-estradiol, with much lesser amounts of estrone. Both compounds occurred as nonconjugates and as glucuronides. beta-Estradiol was not detected in urine. Radiocarbon in feces included primarily alpha-estradiol but also beta-estradiol and estrone, each in non-conjugated form. The fact that most of the intramuscular-administered beta-estradiol was eliminated in the feces strongly suggests a major role for biliary excretion in the disposition of this steroid by steer calves.  相似文献   

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