静注克洛素隆在绵羊体内的药代动力学研究

应用YWG-C18色谱柱(250 mm×4.6 mm,5μm),WatersTM 486型可调波长紫外检测器(检测波长265 nm);0.01 M磷酸钾(pH=7)乙腈(3 1)为流动相;含量测定采用标准曲线法,建立了RP-HPLC法检测绵羊血浆中克洛素隆含量的方法.同时对绵羊单剂量静脉注射7 mg/kg克洛素隆的药代动力学进行了研究.血药浓度在0.005～2.0 μg/ml及2.0～50.0μg/ml范围呈良好线性关系(r=0.9941、0.9970),平均回收率93.2%,血药最低检测浓度0.005μg/ml,日内日间变异系数分别小于10%、11%.血药浓度结果经MCPKP药代动力学统计软件处理,体内药物运转符合三室开放模型,主要药物动力学参数t1/2γ=14.14 h,Kel=0.3260 h-1,AUC=153.95 mg/l@h,fc=0.055.结果表明克洛素隆静脉单次给药后体内分布较为广泛,持续作用时间长,主要通过肾脏排泄.     

克洛素隆注射剂在绵羊体内的药物动力学研究

研究了克洛素隆注射剂在绵羊体内的药物动力学过程。以邻甲苯磺酰胺为内标,建立应用RP-HPLC检测绵羊血浆中克洛素隆含量的方法,血浆浓度在0.01μg/mL~1.0μg/mL及1.0μg/mL~20.0μg/mL范围呈良好线性关系,方法回收率和精密度均能满足药物动力学分析的要求。结果表明,绵羊按4mg/kg单剂量皮下注射克洛素隆,体内药物运转符合二室开放模型。主要药物动力学参数分别为:t1/2Ka=1.355h±0.746h,t1/2β=17.924h±9.186h,tmax=3.181h±1.046h,Cmax=5.121μg/mL±0.997μg/mL,AUC=56.730(mg/L)·h±5.248(mg/L)·h。克洛素隆注射剂皮下注射吸收快,消除较慢,适于绵羊临床寄生虫病的防治。     

国产克洛素隆尿药排泄数据分析

应用Kromasil-C18色谱柱(250 mm×4.6 mm,5 μm),WatersTM480型可调波长紫外检测器,0.01M磷酸钾(pH=7):乙腈(3:1)为流动相,检测波长265 nm,含量测定采用标准曲线法,建立了RP-HPLC法检测绵羊尿中克洛素隆含量的方法.方法有效性评价结果表明,尿药含量在0.01～5.0μg/ml及5.0～30.0μg/ml范围呈良好线形关系(r=0.9993、0.9995),方法平均回收率99.32%,日内、日间变异系数分别为3.91%、6.28%.尿药最低检测限0.005μg/ml.试验绵羊以7 mg/kg单剂量经静脉、肌肉及口服三种途径给药后,尿中药物浓度分析表明,克洛素隆经体内处理后主要经肾脏排泄,给药96 h内,静注经尿排泄原药为81.76%,肌注为64.03%,口服为48.50%.     

硫酸多粘菌素E在猪体内的药代动力学和生物利用度研究

健康断奶仔猪 5头 ,分别进行单剂量肌注 (2 5和 5 0mg/kgb .w .)和静注 (2 5mg/kgb .w .)给药 ,并用微生物学方法对硫酸多粘菌素E在猪体内的药代动力学和绝对生物利用度进行了研究。以 3P97程序处理血药浓度—时间数据 ,结果表明 ,以 2 5和 5 0mg/kgb .w .的剂量肌注给药时 ,其血清中药物的峰浓度 (Cmax)分别为 3 73± 0 2 8μg/ml和 6 40± 0 1 8μg/ml,达峰时间分别为 32 2 2± 1 51min和 34 1 8± 1 76min ,消除半衰期 (t1 / 2 β)为 2 55 99± 1 3 65min和 2 64 0 8± 2 8 57min ;以 2 5mg/kgb .w .的剂量静注给药时 ,其消除半衰期 (t1 / 2 β)为 2 51 2 8± 1 2 53min。静注和肌注在体内的分布均为一级吸收二室模型。肌注 2 5和 5 0mg/kgb .w .剂量的注射液时 ,其平均绝对生物利用度分别为 98 30 %和 88 54 %。     

阿莫西林可溶性粉在猪体内的药代动力学和绝对生物利用度研究

研究阿莫西林可溶性粉在猪体内的药代动力学特征,并评价其与市售注射用阿莫西林钠的生物等效性。采用高效液相色谱法（HPLC）测定血浆中阿莫西林浓度,通过Data Analysis System（DAS 3.0）计算药动学参数,采用非房室模型分析方法对药代动力学参数进行评价,猪经内服给药后,药物平均滞留时间MRT(0-t)为3.12±0.41h,平均达峰时间Tmax为1.63±0.35h,平均达峰浓度Cmax为4101.35±631.55μg/L,平均药-时曲线下面积AUC(0-t)为13540.33±3445.51μg/L×h,消除速率常数λz为0.36±0.14/h,半衰期t1/2z为2.48±1.73h。猪经静脉注射给药后,平均滞留时间MRT(0-t)为1.54±0.35h,平均药-时曲线下面积AUC(0-t)为8522.56±1430.51μg/L×h,消除速率常数λz为0.23±0.12/h,半衰期t1/2z为3.84±2.03h。结果表明：受试制剂阿莫西林可溶性粉经内服给药后,具有较快的吸收速度,吸收进血液后在体内的停留时间较短,代谢较快,平均达峰时间短,药物消除速度较快,平均绝对生物利用度为79.44%,为临床制定合理用药方案提供科学依据。     

头孢噻呋钠在猪体内的药代动力学和生物利用度研究

用微生物杯蝶法测定血清药物浓度,6头实验猪按5 mg/kg单剂量静注、肌注头孢噻呋钠(Ceftiofur Sodium),对其药代动力学和生物利用度进行了研究.试验菌为蜡样芽孢杆菌1.1687,结果平均回收率为96.52%,血清最低检测浓度为0.15 μg/ml,日内日间变异系数为2.5%～4.9%,血清浓度在0.3～0.8 μg/ml范围内呈良好线性关系(r=0.9884).药时数据经Mcpkp药代动力学计算机程序处理,猪静注、肌注头孢噻呋钠体内药物运转都符合二室开放模型,其中静注的药代动力学参数为T1/2α=2.22 h,T1/2β=14.64 h, K12=0.09/h, K21=0.078/h, Kel=0.20/h, V1=0.34 l/kg, VB =1.38 l/kg, CLB=0.07 l/kg/h,AUC=76.56 mg/l*h; 肌注药代动力学参数为Tmax=0.69 h,Cmax=12.09 μg/ml,T1/2ka=0.19 h,T1/2β=15.18 h,Kel=0.23/h,K12=0.14/h,K21=0.08/h;生物利用度为AUCi.m/AUCi.v=87.97%.     

肌肉注射硫酸安普霉素在猪体内的药代动力学和生物利用度研究

对6头健康猪单剂量静脉注射、肌肉注射国产硫酸安普霉素,研究其在猪体内的药代动力学和生物利用度.用微生物法测定血清药物浓度,结果平均回收率为99.03%,血清最低检测浓度为0.05μg/ml,日内日间变异系数为2.2%～5.1%,且血清浓度在0.05～3μg/ml范围呈良好线性关系(r＝0.9965).对猪静注、肌注硫酸安普霉素20mg/kg后,经MCPKP药代动力学计算机程序处理,体内药物运转符合开放型二室模型,肌肉注射0.856h后达峰药浓度Cmax为36.09±1.22μg/ml;t1/2分别为1.58±0.67h、1.06±0.11h,CLB分别为0.15L/kg/h、0.17 L/kg/h,V1分别为0.71L/kg、0.1L/kg,绝对生物利用度为AUC i.m/AUC i.v＝88.47%±3.32%,上述药代动力学数据为动物临床用药提供有价值的理论依据.     

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。     

国产表阿佛菌素在绵羊体内的药代动力学研究

用反相高效液相色谱结合荧光检测法,对试验绵羊经静脉、皮下单剂量注射0 2 mg/kg表阿佛菌素的药代动力学进行了研究。血样提取物通过C18小柱富集、洗脱,甲醇洗提部分经加入1 甲基咪唑和三氟乙酸酐的乙腈液衍生化后进行色谱分析。血药浓度在 2. 5 ~ 200 ng/mL 范围呈良好线性关系(R= 0 996 8),方法平均回收率96 65%±3.84%,血药最低检测限 2.5 ng/mL,日内、日间变异系数分别小于 10%、12%。2 种途径给药后体内药物运转分别符合二室和一室开放模型。主要药代参数如下,静脉注射:消除半衰期(T1/2β)12.66±2.05 h,药时曲线下面积(AUC0~74)1.02±0 30 (mg/L)·h,fc=0 13±0 05; 皮下注射:吸收半衰期(T1/2ka )4.42±1.04 h,峰浓度(Cmax)0 02±0 01 μg/mL,峰时(Tmax ) 15. 36±2. 91 h,消除半衰期(t1/2k ) 26. 22±9. 04 h,药时曲线下面积(AUC0~122)1.19±0 37 (mg/L)·h。上述结果表明,绵羊静脉注射表阿佛菌素后体内药物分布广泛,消除较慢。皮下注射吸收好,消除比静脉注射更为缓慢,体内药物平均滞留时间长。     

口服硫酸安普霉素在猪体内的药代动力学和生物利用度研究

对 5头健康猪口服和静脉注射国产硫酸安普霉素 ,研究其在猪体内的药代动力学和生物利用度。用微生物法测定血清药物浓度 ,结果平均回收率为 99.0 3%,血清最低检测浓度为 0 .0 5 μg/ ml,日内日间变异系数为 2 .2 %～ 5 .0 %,且血清浓度在0 .0 5～ 3μg/ m l范围呈良好线性关系 (r=0 .996 5 )。以 2 0 mg/ kg口服和以 2 0 mg/ kg静脉注射硫酸安普霉素后 ,经 Mcpkp药代动力学计算机程序处理 ,体内药物运转分别符合开放型一室和二室模型 ,生物半衰期 t1 / 2 分别为 (7.36± 1 .5 2 ) h和 (3.1 7± 0 .75 )h;CLB分别为 4 .82 L / kg· h和 0 .1 6 L / kg· h;AUC值分别为 4 .1 4和 1 30 .6 2。口服 :Cmax为 (0 .2 4± 0 .0 3)μg/ ml;Tp为 (5 .1 2±0 .6 1 ) h;T1 / 2 K为 (7.36± 1 .5 2 ) ;生物利用度 (AUCp.0 / AUCi.v)为 (3.1 92 8± 0 .70 4 4 ) %。上述药代动力学数据为动物临床用药提供有价值的理论依据     

单诺沙星在蛋雏鸡体内的药物动力学及生物利用度的研究

选用 4～ 5周龄健康蛋雏鸡 12 5只 ,按 5 mg/kg的剂量进行静脉注射和内服单诺沙星的药动学研究及生物利用研究。高效液相色谱内标法测定血浆中药物浓度 ,MCPKP药动学程序处理药时数据。静脉注射和内服给药后血药浓度—时间数据分别符合无吸收因素二室开放式模型和一级吸收一室开放式模型。静脉注射给药的主要药动学参数为 :t1 /2α=0 .3313h、t1 /2β= 5 .994 0 h、Vd=7.5 2 4 6 L/kg、AU C=5 .6 916 μg/m l· h、CLB=0 .8935 L/kg· h。内服给药后主要药动学参数为 :t1 /2 Ka=0 .30 2 9h、t1 /2 K=6 .5 12 8h、tmax=1.2 10 0 h、Cmax=0 .5 15 9μg/m l、AU C=5 .132 9μg/ml· h。生物利用度为 90 .18%。     

盐酸沙拉沙星在兔体内的药物动力学及生物利用度研究

选用24只健康哈白兔，分3组，每组8只，进行药物动力学研究。静注、内服和肌注剂量均为10mg/kg。以反相高效液相色谱法，测定了血清中的药物浓度，所得药时数据用MCPKP程序处理，得出了药动学参数，拟合方程及肌注和内服的生物利用度。结果表明，哈白兔静注盐酸沙拉沙星后的药时数据符合无吸收因素二室模型，主要药动学参数如下Vd4.67±0.75L/kg，t1/2α0.54±0.12h，t1/2β4.43±0.186h，AUC13.86±2.63μg/ml*h，ClB0.75±0.16L/kg*h。兔内服盐酸沙拉沙星后，药时数据符合一级吸收一室开放式模型，主要药动学参数如下t1／2ka0.36±0.08h，t1/2Kel5.94±1.09h，tmax1.53±0.15h，cmax0.41±0.09μg/ml,AUC4.19±0.86μg/ml*h，生物利用度为30.22%。兔肌注盐酸沙拉沙星后，药时数据符合一级吸收二室开放式模型，主要药动学参数如下t1/2ka0.06±0.01h，t1/2α0.83±0.16h，t1/2β5.01±1.14h，AUC10.75±1.38μg/ml*h，tmax0.27±0.02h，cmax3.52±0.38μg/ml，生物利用度为77.58%。     

Prophylactic efficacy of clorsulon against Fasciola hepatica in calves and sheep

A daily oral 5 mg kg-1 dose of clorsulon for 28 days in calves given Fasciola hepatica cysts at 3, 5, and 7 days after initiation of treatment was highly effective in reducing worm burdens (98%) and preventing liver pathology. In similarly infected and treated sheep, clorsulon showed little effect as a prophylactic for delaying the onset of liver pathology. The size of flukes recovered from treated sheep was reduced. Although clorsulon prevented development of fascioliasis in treated calves, the host antibody response was qualitatively similar to that of untreated infected calves, but the magnitude of the response was reduced. Blood clorsulon levels in calves rose to 2.90 micrograms ml-1 within the first week of treatment then fluctuated between 2.65 and 2.90 micrograms ml-1 for the next two weeks. Clorsulon levels in sheep were 0.50-0.60 micrograms ml-1 lower than those in calf blood. The difference in bioavailability of clorsulon between sheep and calves may have contributed to differences in efficacy of the drug.     

Efficacy of clorsulon against Fascioloides magna infection in sheep

In a study to evaluate the efficacy of clorsulon against Fascioloides magna infection in sheep, 12 ewes were inoculated orally with 100 metacercariae of F magna, and 6 were treated with clorsulon (15 mg/kg of body weight) 8 weeks after inoculation. The sheep were euthanatized 16 weeks after inoculation, flukes were recovered, and the liver and other tissues were subjectively scored for the severity of lesions (0 to 4+). The number of flukes recovered from the clorsulon-treated group (3.8 +/- 1.2 flukes) was significantly (P = 0.025) lower than the number of flukes recovered from the group of untreated controls (10.0 +/- 6.6 flukes). The severity of lesions was significantly (P = 0.004) reduced (45.9%) in the treated group (2.0 +/- 1.1), compared with that in the untreated controls (3.7 +/- 0.5). In the untreated group, 3 sheep died and 1 became moribund 14 to 16 weeks after inoculation. The data suggested that a single treatment with clorsulon at a dosage of 15 mg/kg 8 weeks after inoculation was not effective in preventing F magna infection in sheep, because the survival of only a few F magna is potentially fatal in sheep within 6 months after infection.     

Evaluation of clorsulon against immature Fascioloides magna in cattle and sheep

Efficacy of clorsulon was evaluated against infection with immature Fascioloides magna in 24 cattle and 12 sheep. Infections were induced by oral administration of 600 metacercariae/host. In cattle, clorsulon at dosages of 7 and 21 mg/kg of body weight was 65 and 100% effective against 8-week-old flukes, and 20 and 74% effective against 16-week-old flukes, respectively. In sheep, clorsulon at a dosage of 21 mg/kg was 92% effective against 8-week-old flukes. Significantly (P less than 0.05) more F magna were recovered from untreated sheep than from untreated cattle.     

Levamisole pharmacokinetics and bioavailability in dogs

Levamisole was given intravenously and orally (with and without food) to six dogs. All dogs reacted adversely to intravenous dosage and one died. For the remaining five, intravenous data fitted a one compartment model with first order elimination and a mean half-time of elimination of 1.8 hours. In fasting dogs drug absorption from the gut was rapid and the mean fraction absorbed (F) was 0.64. When levamisole was given with food, drug bioavailability was impaired, as absorption was slowed and possibly reduced (F = 0.49). The effect of ingesta on bioavailability of levamisole could affect treatment efficacy and side effects.     

儿茶素在家兔体内的生物利用度及药物动力学研究

选健康家兔 ,单剂量静注和灌服儿茶素 (Catechin) 2 5 mg/ kg,用高效液相色谱法测定其血药浓度 ,3P87计算机程序处理所得血药浓度—时间数据。结果健康家兔静注给药的药时数据符合无吸收二室开放模型 ,主要动力学参数为 :t1 /2α(0 .15± 0 .0 1) h,t1 /2β(0 .5 8± 0 .0 2 ) h,Vc (1.4 1± 0 .0 8) l,Vβ(2 .97± 0 .11) l,Cl B(3.5 3±0 .10 ) l/ h,AU C(16 .95± 1.5 2 ) mg/ (l· h) ,K1 0 (2 .5 2± 0 .2 0 ) h- 1 ,K2 1 (2 .2 5± 0 .15 ) h- 1 ,K1 2 (1.17± 0 .15 )h- 1 。健康家兔灌服儿茶素的药时数据符合一级吸收一室开放模型 ,主要药物动力学参数为 :t1 /2 ka(0 .39± 0 .0 6 )h,t1 /2 ke(0 .79± 0 .11) h,tmax(0 .78± 0 .11) h,Cmax(3.35± 0 .16 ) mg/ l,AU C (7.4 5± 0 .94 ) m g/ (l· h) ,F (6 4±7.0 0 ) %。儿茶素在健康家兔体内的药动学特征是 :吸收迅速 ,达峰时间短 ,消除快 ,半衰期短 ,表观分布容积较大 ,口服摄入吸收不完全     

Thalidomide pharmacokinetics in sheep

AIM: To determine the half life (T_1/2), time taken to reach maximum plasma concentration (T_max) and maximum plasma concentration (C_max) of thalidomide in sheep following I/V, oral and topical treatment with a single dose of thalidomide.

METHOD: Three groups of 4–6-month-old ram lambs were treated with thalidomide dissolved in dimethylsulphoxide (DMSO). The first group (n=10) was treated I/V with 100?mg thalidomide in 2?mL DMSO; the second group (n=8) received 400?mg thalidomide in 2?mL DMSO orally, and the third group (n=8) had 400?mg thalidomide in 4?mL DMSO applied topically. Plasma samples were collected up to 36 hours after treatment, snap-frozen at ?80°C and analysed for concentrations of thalidomide using high performance liquid chromatography.

RESULTS: Following I/V administration, T_1/2 was 5.0 (SEM 0.4) hours, volume of distribution was 3,372.0 (SEM 244.3) mL/kg and clearance was 487.1 (SEM 46.1) mL/hour.kg. Topical application of 400?mg thalidomide did not increase plasma concentrations. Following oral administration, thalidomide bioavailability was 89%, with T_1/2, T_max, and C_max being 7.2 (SEM 0.8) hours, 3.0 (SEM 0.4) hours and 1,767.3 (SEM 178.1) ng/mL, respectively.

CONCLUSION: Topical administration using DMSO as a solvent did not increase concentrations of thalidomide in plasma. The mean pharmacokinetic parameters determined following oral treatment with 400?mg of thalidomide were similar to those reported in humans receiving a single 400?mg oral dose (T_1/2 7.3 hours; T_max 4.3 hours and C_max 2,820?ng/mL). There is potential for thalidomide to be used as a model for the treatment of chronic inflammatory conditions in sheep, such as Johne's disease, where tumour necrosis factor alpha plays a pathogenic role.     

Thiamphenicol pharmacokinetics in sheep

Abdennebi, E.H., Khales, N., Sawchuk, R.J., Stowe, CM. Thiamphenicol pharmacokinetics in sheep. J. vet. Pharmacol. Therap. 17, 12–16.
The pharmacokinetics of thiamphenicol were investigated after intravenous (i-v.). intramuscular (i.m.) and oral (p.o.) administration to sheep. It was found that the drug is almost completely absorbed following intramuscular injection, with a bioavailability of about 8 7.5%. Thiamphenicol appears to be widely distributed into extravascular compartments, yielding a volume of distribution [V(b)] of approximately 1 1/Kg. Elimination from the blood is relatively rapid, with a biological half-life of about 1.5 h. Oral treatment showed that thiamphenicol is absorbed from the gastrointestinal tract yielding very low plasma concentrations which were maintained for at least 24 h. Although only 30% of the oral dose was systemically available, in contrast to chloramphenicol, thiamphenicol is truly absorbed when given orally to adult sheep. One possible reason for this observation is that rumen flora do not biotransform this drug as they do for chloramphenicol. Metabolism investigations are, however, needed to confirm this finding.