青霉素G钠在家兔体内组织动力学与残留的研究

采用高效液相色谱(HPLC)法研究了青霉素G钠在家兔多种组织中的动力学过程。家兔单剂量肌注青霉素G钠后,青霉素G钠在组织中的经时过程:肝、肾、心符合一级吸收的三项指数方程,肺、肌肉符合一级吸收的二项指数方程。青霉素G钠的组织浓度顺序为肾>肺>心>肌内>肝。用药后组织中药物浓度下降至0.01ppm所需时间,肝、肾、心、肺、肌肉分别为24.862、14.842、10.208、4.074、16.743小时。青霉素G钠在兔体内的最短休药期为1.5天。     

喹乙醇在肉鸡体内的组织动力学与残留的研究

研究了喹乙醇在肉鸡体内的组织动力学过程及在组织中的残留。并对血药和组织药物浓度进行动态相关分析。结果表明,药物按一级速率过程从组织中消除,药物在心、肝、肾、肌肉各组织中的半衰期分别为1.96、2.89、3.11、1.77小时。药物在各组织中的残留时间以肾脏最长、肌肉最短。     

烟酸诺氟沙星在猪,鸡体内的组织残留研究

本文报道了烟酸诺氟沙星在猪、鸡体内的组织残留研究结果，猪、鸡均按１０ｍｇ／ｇ剂量给药，采用ＨＰＬＣ法测定肝、肾、肌肉中诺氟沙星浓度。猪肌注给药后７２小时，肾。肌肉中药物浓度已低于仪器最低检测限（０．０５μｇ／ｇ），肝中仍能检出少量药物，浓度为０．３０５±０．１６９μｇ／ｇ；鸡口服给药后４８小时，肝、肾、肌肉中药物浓度均已低于最低检测限。根据本试验结果，建议猪、鸡使用烟酸诺氟沙星后休药期为６天和２天。     

土霉素在斑节对虾体内药代动力学和生物利用度

在自然海水（盐度33）．水温为（28．0±1．0）℃养殖条件下,采用反相高效液相色谱法（RP—HPLC）,研究口灌（100mg／kg）和围心腔注射（20mg／kg）2种给药途径下,土霉素在斑节对虾（Penaeus7YlOylodoYl）体内的药代动力学和生物利用度。围心腔注射和口灌给药下,血药药时曲线均适合采用二室模型拟合。围心腔注射下血药达峰浓度（Cmax）、药时曲线下面积（AUC0-1）、消除半衰期（t,m）分别为（80．71±13．12）mg／L 378．25nag·h·L-1、17．398h;口灌给药下的相应值分别为（21．98±3．32）mg／I。324．52nag·h·L-1、23．372h,土霉素在斑节对虾体内的生物利用度（F）为17．16％。口灌土霉素后,肝胰腺Cmax为（138．655±21．375）μg／g,是血药的6．3倍、肌肉峰浓度的130．2倍,药物在肝胰腺中含量最高;然而。肌肉和肝胰腺中土霉素消除较快,消除半衰期（t1/2x）分别为28．18h和19．311 h。根据我国水产品中药物残留限量规定,水产品中土霉素的最高残留限量（NY5070—2002）为0．1mg／kg,结合本试验研究结果,斑节对虾使用土霉素后的休药期为5d,肌肉可食组织即符合无公害食品标准要求。     

延边黄牛ANGPTL4基因组织表达规律与肌内脂肪沉积相关性研究

为分析ANGPTL4基因在延边黄牛各组织中的表达差异,进一步探讨该基因在肌内脂肪沉积中的作用,本实验利用q RT-PCR法比较分析了ANGPTL4基因在延边黄牛7个组织(心、肝、脾、肺、肾、背最长肌和后腿肌)中的表达水平及其与肌内脂肪沉积的相关性。结果表明:ANGPTL4基因在7个组织中表达水平从高到低依次为肝、肺、肾、心、脾、背最长肌和后腿肌,肝中表达量极显著高于心、脾、肺、肾、后腿肌和背最长肌组织(P0.01),肺中表达量显著高于心、脾、肾、后腿肌和背最长肌组织(P0.05);背最长肌中ANGPTL4基因的表达量与背最长肌的IMF含量呈显著正相关(P0.05),相关系数为0.924;ANGPTL4基因在后腿肌的表达量与后腿肌的IMF含量呈显著正相关(P0.05),相关系数为0.998。结果显示,ANGPTL4基因影响延边黄牛肌内脂肪沉积。     

丙硫咪唑在鸡体内的药代动力学及组织残留的研究

给鸡单剂量口服丙硫咪唑(15mg/kg),用HPLC法测定不同时间的鸡体内药物及其代谢物的浓度.结果,在血浆和组织中均未发现丙硫咪唑,而其两个代谢物丙硫咪唑亚砜(亚砜)和丙硫咪唑砜(砜)在血浆中的药代动力学行为符合方程:C(亚砜)=22.3581(e~(-0.142(t-0.6053))-e~(-0.4505(t-0.8053)));C(砜)=4951.7774(e~(-0.2769(t-0.9111))-e~(0.278(t-0.9111)))。亚砜和砜的主要药动学参数分别为:消除相半衰期(t1/2ke)为4.87和2.57h,表观分布容积(Vd)为0.98和0.76L/kg,峰时间(Tm)为4.34和4.52h,峰浓度(Cm)为8.98和7.22μg/mL。亚砜在心、肝、胰、肺、肾等组织中的残留量:给药后3d分别为1.14、5.35、2.42、1.78、2.45μg/g;5d分别为0.281.79、2.34、1.13、1.16μg/g;7d分别为0.12、0.68、1.69、0.48、0.69μg/g.砜在上述组织中的残留量:给药后3d分别为3.15、10.44、8.16、0.99、2.83μg/g;5d分别为1.53、1.04、4.11、0.86、0 89μg/g;7d分别为:0.77、0.67、2.09、0.53、0.12μg/g。     

重组溶葡萄球菌酶泡腾栓在母猪体内的药动学与阴道内残留消除研究

通过双抗夹心酶联免疫学方法,采用药代动力学软件3p97,分别在健康和患阴道炎猪体进行重组溶葡萄球菌酶(rLSP)药代动力学及阴道黏液中活性研究分析,对静脉注射rLSP的药物浓度-时间数据进行最佳模型拟合。结果表明,健康和患阴道炎母猪经静脉注射rLSP(400U)后,消除半衰期分别为36.10分钟和40.36分钟。健康和患阴道炎母猪经阴道给药rLSP泡腾栓(400U)后,试验母猪血液中均未检测到酶活性,说明rLSP经阴道内黏膜吸收后在血液中没有药物蓄积。健康母猪和患病母猪在给药后36小时阴道内黏液中均能检测到酶活性(分别为7.34ng/mL和4.45ng/mL),而在第48小时均未检出,表明该药物在阴道内至少保持36小时的活性,且作用48小时后无残留。     

氨苄西林在鸡组织中的残留消除规律

旨在研究氨苄西林在鸡组织中残留消除规律。鸡组织样品经磷酸二氢钠溶液提取,乙腈去蛋白质,正己烷去脂肪,饱和二氯甲烷萃取,上清液经甲醛在酸性条件下沸水浴衍生化后,在激发波长327nm、发射波长409nm处用高效液相色谱荧光检测器检测。结果显示:该方法测定鸡组织中氨苄西林的检测限为3.5μg·kg-1(S/N=3)、定量限为10.0μg·kg-1(S/N=10)。氨苄西林在鸡组织样品中平均回收率在75.31%~85.87%,变异系数均低于10.20%。各试验组京海黄鸡分别按体重以120、240mg·(kg·d)-1剂量内服氨苄西林,每天1次,连续7d给药后,休药4h(零休药期),各组织中氨苄西林的残留量最高,并在休药后第3天迅速降低。休药第5天后所有组织中氨苄西林残留量均低于最高残留限量(50μg·kg-1),休药第9天各组织中氨苄西林残留量均低于检测限。休药后相同时间点鸡肌肉中药物残留量最低,肝中的药物残留量最高;氨苄西林在肾中残留比肌肉、肝消除缓慢且消除时间长。氨苄西林在鸡肌肉、肝和肾中的残留量均与给药剂量呈正相关。根据WT1.4软件按95%置信区间计算所得,建议黄羽肉鸡按体重以120、240mg·(kg·d)-1剂量给药,每天1次,连续7d后,其休药期(WT)分别为4和5d。     

日粮钙、锌水平对蛋鸡肝脏和肾脏金属硫蛋白含量的影响

本研究由两个实验组成,分别观察了不同钙、锌日粮水平下,肝脏和肾脏细胞浆内金属硫蛋白(MT)含量的动态变化.实验1,在含锌30.2～30.8ppm的大豆—玉米型基础日粮中,分别添加0.72%、3.0%和6.0%的钙,其中3%钙组在实验第220d后,在日粮中添加40ppm锌,继续饲喂9d.实验2,在基础日粮中分别添加1000ppm、2OO0ppm、4O00ppm和4000ppm锌,饲喂13d,其后,第4组(日粮中添加4000ppm锌组)改喂基础日粮.结果如下:实验1,各组肝脏和肾脏锌含量均显著低于实验前的水平,其中6%钙组尤为明显;各组肝、肾细胞浆中MT含量均<0.6ppm,且与其组织锌含量呈正相关;3%钙组添加40ppm锌后,肝、肾锌及MT含量迅速增加,明显高于添加前的水平.由此表明,高钙日粮干扰了肝、肾锌的代谢和MT的合成.实验2,肝、肾锌及MT含量与锌的添加水平及接触锌的时间长短有关,锌含量与MT的变动呈正相关,且MT的增高幅度显著大于锌;切断外加锌源后,肝、肾锌及其MT含量迅速减少,其衰减期分别为9(5～10)和6(5～7)d;MT含量的变动与其他含锌蛋白亦有一定关联.实验2表明,肝脏是合成及贮存NT的主要器官,其效能强于肾脏,MT含量能准确反映体内锌状态.     

透皮给药后吡喹酮在小鼠体内组织分布及药代动力学

目的研究透皮给药后吡喹酮在小鼠体内的组织分布及药代动力学。方法用200mg/mL吡喹酮透皮剂涂擦小鼠腹部后,采用高效液相色谱法检测各时间点小鼠器官(肝、心脏、脾和肾)的吡喹酮浓度,分析其在各器官药代谢动力学特点。结果透皮给药后吡喹酮在小鼠肝脏分布浓度最高,脾和肾次之,心脏的浓度最低。吡喹酮在小鼠肝脏、脾和肾脏c-t曲线,各出现两个峰值,第一个峰值4min,Cmax分别为31.78μg/mL和7.87μg/mL,第二个峰值15min,Cmax分别为27μg/mL,11.1μg/mL。小鼠心脏的c-t曲线,有一个峰值3min,Cmax3.91μg/mL。结论吡喹酮透皮给药后,在小鼠肝脏分布浓度高,达到了临床治疗的要求。     

The distribution of oxytetracycline in the tissues of Swine following a single oral dose

A single oral dose of oxytetracycline hydrochloride (50 mg/kg) produced detectable residues in the following tissues; adrenal, bile, fat, heart, kidney (cortex), kidney (medulla), liver, lung, lymph node (mesenteric), muscle, serum, spleen, thyroid and urine. The highest residue levels were observed in the urine (441 μg/mL) at three hours after administration and they were still present at 48 hours. Maximum serum levels were observed at two hours after administration. Bile samples were positive for inhibitors in all animals sampled. Drug residues were not detected in spleen, thyroid, lymph node, adrenals and heart at 48 hours.

Drug levels in important edible tissues were expressed as a percentage of drug levels in two tissues with high drug concentrations — urine and kidney cortex. The percentages were highly variable when compared with urine and much less variable when compared to kidney cortex.

Kidney cortex appears to be an excellent tissue for drug residue monitoring.

     

Enramycin在鸡体内残留分析研究

本文报道了Ｅｎｒａｍｙｃｉｎ在鸡体内的残留分析结果。供分析的组织经胃蛋白酶消化，甲醇及盐酸混合液抽提，ＸＡＤ－２柱分离杂质、薄层层析及枯草杆菌ＡＴＣＣ６６３３生物显像，进行定性及定量分析。此法在肝、肾、肌肉、脂肪组织和血中Ｅｎｒａｍｙｃｉｎ的回收率分别为５７．７０％、４６．６５％、４４．８０％、３９．３５％及４６．６０％，其敏感度为２５ｐｐｂ。测试样来自喂饲１０ｐｐｍ Ｅｎｒａｍｙｃｉｎ８周的试验     

乙酰甲喹及其主要代谢物在鸡体内的残留消除规律研究

建立了高效液相色谱串联质谱（HPLC—MS／MS）法用于乙酰甲喹及其6种主要代谢物的检测。将65只健康白羽鸡分为两组,10只为空白对照组,其余为试验组。试验组施以20mg／kgb．w．灌胃乙酰甲喹悬浊液,1d2次,连续3d。在给药结束后2、4、6、12、16、24、30、36、48、72、120h分别宰杀5只鸡,采集血液和可食性组织（肌肉、肝脏、肾脏和皮脂）样品。结果表明：乙酰甲喹原药在组织和血浆中迅速消除;乙酰甲喹的代谢物广泛存在于鸡的可食性组织和血浆中;代谢物的残留消除过程较为复杂,代谢物在肌肉和肝脏中残留量较多,在皮脂中残留时间最长。研究结果将有助干榍示7．酷甲喹存鸡体内的砖留消除期,律．     

Pharmacokinetics of amoxycillin and the rate of depletion of its residues in pigs

Six pigs were used in a two-period crossover study to investigate the pharmacokinetics of amoxycillin after single intravenous and oral doses of 20 mg/kg bodyweight. Twelve pigs were used to study the residues of the drug in muscle, kidney, liver and fat after they had received daily oral doses of 20 mg/kg amoxycillin for five days. The mean (sd) elimination half life (t1/2beta) and mean residence time of amoxycillin in plasma were 3.38 (0.30) and 3.54 (0.43) hours, respectively, after intravenous administration and 4.13 (0.50) and 4.47 (0.30) hours, respectively, after oral administration. After oral administration, the maximum plasma concentration (Cmax) was 7.37 (0.42) microg/ml and it was reached after 0.97 (0.29) hours. Six days after the last oral dose, the mean concentration of amoxycillin in the pigs' kidneys was 21.38 ng/g and in the liver it was 12.32 ng/g, but no amoxycillin could be detected in fat or muscle; the concentrations of amoxycillin in edible tissues were less than the European Union maximal residue limit of 50 microg/kg.     

Acute toxicity of boric acid and boron tissue residues after chronic exposure in broiler chickens.

The acute oral mean lethal dose of boric acid in 1-day-old chickens was found to be 2.95 +/- 0.35 g/kg of body weight, which classifies this product as only slightly toxic to chickens. One-day-old broiler chicks were housed in floor pens in which litter had been treated with 0, 0.9, 3.6, or 7.2 kg of boric acid per 9.9 m2 of floor space. Boron residue levels in brain, kidney, liver, and white muscle were not statistically elevated following a 15-day exposure period. Boron residue levels in the same types of tissue were not significantly elevated in chicks fed 500 ppm or 1250 ppm boric acid in feed ad libitum for 3 weeks; however, residues were significantly higher in chicks fed 2500 ppm or 5000 ppm boric acid. These data indicate that broilers grown on boric acid-treated litter do not consume enough boric acid to cause elevated boron levels in tissues.     

Comparative plasma and tissue pharmacokinetics and drug residue profiles of different chemotherapeutants in fowls and rabbits

Blood and tissue pharmacokinetics and drug residue profiles of six chemotherapeutants were studied. Ceftriaxone (CEF), intravenously at 50 mg/kg, sulfamonomethoxine (SMM) and sulfaquinoxaline (SQ), orally at 200 mg/kg, and olaquindox (OLA), orally at 50 mg/kg, were administered to young broilers. Penicillin (PEN), intramuscularly at 200 000 U/kg, and albendazole (ALB), orally at 20 mg/kg, were given to rabbits. For each drug, 13–18 groups ( n = 5–10 individuals/group) of the dosed animals were killed at different post-dosing times. Drug and/or metabolite concentrations in plasma, liver, kidney, heart, lung, and muscle tissues were analysed by HPLC procedures. Multi-exponential kinetic models were fitted to the observed tissue concentration-time data by applying a non-linear least-squares regression computer program. Tissue half-life, peak tissue concentration, and time of peak tissue concentration were determined. Half-life of CEF, SMM, SQ, OLA, PEN, ALB, and two metabolites of ALB (sulfoxide and sulfone) in various tissues ranged 0.6–1.4, 4.7–9.0, 4.5–18.9, 1.8–3.1, 0.9–3.0, 3.4–9.6, 5.0–16.1 and 7.4–12.2 h. The times required for CEF, SMM, SQ, OLA, PEN, and ALB residue concentrations to decline to 0.1 μg/g in various tissues ranged from 5.0–11.6. 70.0–110.5. 114.0–179.8, 21.3–30.3,4.1–24.8 and 47.8–84.4 h. Drug kinetic characteristics in tissues differed significantly from those in plasma, and also varied from tissue to tissue. It is necessary, therefore, to evaluate tissue kinetics when designing dosage regimens in tissue infection chemotherapy with these drugs. Knowledge of tissue kinetics is also important in predicting and controlling drug residues in edible tissues of food-producing animals.     

三聚氰胺在肉鸡组织中的残留和消除规律研究

本试验旨在研究日粮中三聚氰胺在肉鸡不同组织中的残留和消除规律。选用1日龄健康黄羽肉鸡400只,随机分成4个处理,每处理设5个重复,每个重复20只鸡。试验日粮中三聚氰胺的添加量分别为0%、0.25%、0.5%、和3.0%,连续饲喂42d,后改喂基础日粮。于残留试验第7、14、21、28、35和42天和改喂基础日粮的第1、2、3、4和5天分别测定肉鸡肾脏、肝脏和胸肌中的三聚氰胺含量。结果表明,黄羽肉鸡连续饲喂含三聚氰胺日粮42d,处理组各组织中三聚氰胺平均含量均显著高于对照组(P<0.05);3.0%处理组各组织中三聚氰胺含量的高低依次为:肾脏>肝脏>胸肌。组织中三聚氰胺消除较为缓慢,日粮含量越高组织中三聚氰胺消除速率越快。改喂基础日粮5d后,各组织中的三聚氰胺含量显著降低,逐渐接近对照组值,但5d各组织中三聚氰胺含量均未消除完全。日粮三聚氰胺含量越高,肉鸡组织中的残留浓度越高,消除需要的时间越长。     

A physiologically based pharmacokinetic model for valnemulin in rats and extrapolation to pigs

A flow-limited, physiologically based pharmacokinetic (PBPK) model for predicting the plasma and tissue concentrations of valnemulin after a single oral administration to rats was developed, and then the data were extrapolated to pigs so as to predict withdrawal interval in edible tissues. Blood/tissue pharmacokinetic data and blood/tissue partition coefficients for valnemulin in rats and pigs were collected experimentally. Absorption, distribution and elimination of the drug were characterized by a set of mass-balance equations. Model simulations were achieved using a commercially available software program. The rat PBPK model better predicted plasma and tissue concentrations. The correlation coefficients of the predicted and experimentally determined values for plasma, liver, kidney, lung and muscle were 0.96, 0.94, 0.96, 0.91 and 0.91, respectively. The rat model parameters were extrapolated to pigs to estimate valnemulin residue withdrawal interval in edible tissues. Correlation (R(2) ) between predicted and observed liver, kidney and muscle were 0.95, 0.97 and 0.99, respectively. Based on liver tissue residue profiles, the pig model estimated a withdrawal interval of 10 h under a multiple oral dosing schedule (5.0 mg/kg, twice daily for 7.5 days). PBPK models, such as this one, provide evidence of the usefulness in interspecies PK data extrapolation over a range of dosing scenarios and can be used to predict withdrawal interval in pigs.     

Pharmacokinetic and tissue residue characteristics of fenprostalene, a prostaglandin F2 alpha analog, in swine

Fenprostalene, a prostaglandin F2 alpha analog, can be used to induce parturition in swine. As part of the approval process for that indication, pharmacokinetic characteristics of the absorption and elimination of fenprostalene and the depletion of drug residues from the principal edible tissues of swine were studied. Blood samples, urine, and feces were collected from 8 gilts (body weight, 95 +/- 1.7 kg) for up to 72 hours after a single dose of 0.5 mg of 13,14-[3H]-fenprostalene in polyethylene glycol-400 was administered SC. At intervals of 24, 48, 72, and 168 hours after dosing, 2 gilts each were killed, and samples of liver, kidney, muscle, and abdominal fat were obtained for analysis. The mean (+/- SEM) maximal concentration of fenprostalene radioequivalents in plasma (0.41 +/- 0.05 nanogram-equivalents/ml; n = 8) was observed at 12 hours and decreased biexponentially, with half-lives of approximately 8 hours and 9 days. Mean cumulative recovery (n = 4) of the administered dose by 72 hours was 61.2 +/- 5.9% in urine and 18.5 +/- 2.6% in feces. The highest tissue fenprostalene concentration was in kidneys and liver, probably reflecting the role of those organs in excreting fenprostalene. Rates of depletion of fenprostalene equivalents from the injection site, kidneys, and liver were comparable with those previously observed in cattle. The composition of residue in the liver of 2 gilts slaughtered 12 hours after SC administration of [3H]-fenprostalene was examined in a second study. Results suggested that approximately 4% of the total residue was pharmacologically potent fenprostalene or the carboxylic acid form of fenprostalene.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxytetracycline pharmacokinetics, tissue depletion, and toxicity after administration of a long-acting preparation at double the label dosage

Oxytetracycline (OTC) concentration in plasma and tissues, plasma pharmacokinetics, depletion from tissue, and toxicity were studied in 30 healthy calves after IM administration of a long-acting OTC preparation (40 mg/kg of body weight) at double the label dosage (20 mg/kg). Plasma OTC concentration increased rapidly after drug administration, and by 2 hours, mean (+/- SD) values were 7.4 +/- 2.6 micrograms/ml, Peak plasma OTC concentration was 9.6 +/- 2.6 micrograms/ml, and the time to peak plasma concentration was 7.6 +/- 4.0 hours. Plasma OTC concentration decreased slowly for 168 hours (elimination phase) after drug administration, and the elimination half-life was 23.9 hours. Plasma OTC concentration exceeded 3.8 micrograms/ml at 48 hours after drug administration. From 168 to 240 hours after drug administration, plasma OTC concentration decreased at a slower rate than that seen during the elimination phase. This slower phase was termed the depletion phase, and the depletion half-life was 280.7 hours. Tissue OTC concentration was highest in kidneys and liver. Lung OTC concentration exceeded 4.4 micrograms/g of tissue and 2.0 micrograms/g of tissue at 12 and 48 hours after drug administration, respectively. The drug persisted the longest in kidneys and liver. At 42 days after drug administration, 0.1 micrograms of OTC/g of kidney was detected. At 49 days after drug administration, all OTC tissue concentrations were below the detectable limit. Reactions and toxicosis after drug administration were limited to an anaphylaxis-like reaction (n = 1) and injection site swellings (n = 2).