替米考星在绵羊体内的药代动力学研究

5只健康小尾寒羊，采用静脉和皮下注射2种途径以替米考星10mg/kg体重剂量给药，进行体内药代动力学研究。动物给药后在96h内分点采血，血浆样品处理采用甲醇沉淀，离心去蛋白，调节pH值并用氯仿提取替米考星；样品测定采用苯基柱，以反向HPLC测定绵羊血清中的替米考星浓度。结果表明，绵羊静注和皮下注射替米考星的药时数据均符合二室开放模型，替米考星皮下注射和静脉给药在羊体内具有吸收和分布较迅速，消除缓慢，体内分布容积大，生物利用度较高的特点。结果对了解替米考星在绵羊体内的药动学特征以及指导临床正确用药具有重要意义。     

二甲苯胺噻唑在绵羊脑脊液中的药物动力学研究

以内标气相色谱法为定量手段，研究二甲苯胺噻唑在绵羊脑脊液（ＣＳＦ）中的药动力学。实验结果表明，绵羊肌注二甲苯胺噻唑（２．５ｍｇ／ｍｌ）后，ＣＳＦ药物经时特征主要符合一级吸收单室开放模型，部分符合一级吸收双室开放模型，其主要药动学参数：吸收半衰期为３．８６８±１．４５２ｍｉｎ，消除半衰期为１４０．３３８±１１０．０３８ｍｉｎ，ＣＳＦ药浓度达峰时间为１７．６３７±５．８５０ｍｉｎ，ＣＳＦ药峰浓度为０．     

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。     

Pharmacokinetics of Amoxicillin Trihydrate in Desert Sheep and Nubian Goats

The pharmacokinetics of amoxicillin were studied in five Desert sheep and five Nubian goats after intravenous (i.v.) or intramuscular (i.m.) administration of a single dose of 10 mg/kg body weight. Following i.v. injection, the plasma concentration-versus-time data were best described by a two-compartment open model. The kinetic variables were similar in both species except for the volume of the central compartment (V_c), which was larger in sheep (p<0.05). Following i.m. injection, except for the longer half-life time of absorption in goats (p<0.05), there were no significant differences in other pharmacokinetic parameters between sheep and goats. The route of amoxicillin administration had no significant effect on the terminal elimination half-life in either species. The bioavailability of the drug (F) after i.m. administration was high (>0.90) in both species. These results indicate that the pharmacokinetics of amoxicillin did not differ between sheep and goats; furthermore, because of the high availability and short half-life of absorption, the i.m. route gives similar results to the i.v. route. Therefore, identical intramuscular and intravenous dose regimens should be applicable to both species.     

替米考星静脉及皮下注射后在绵羊体内的药代动力学研究

健康成年杂交绵羊静脉和皮下注射替米考星注射液后,用反相高效液相色谱法测定不同时间点血清中的药物浓度。采用3p97药代动力学程序软件处理数据,替米考星两种给药途径的药 时数据均符合二室开放模型静脉注射给药(5 mg/kg bw)的主要药代动力学参数: t1/2a 为 0. 611±0. 017 h、t1/2β为 23. 215±0. 459 h、AUC为11 815±0.396(μg/mL)·h、CL(s)为 0.424±0.014 L/(kg·h)。替米考星皮下注射主要药代动力学参数: 1mg/kg bw剂量组 t1/2a 为 1 751±0 557 h、t1/2β为 22 896±2 747 h、t1/2Ka 为 0. 100±0. 025 h、AUC 为 25. 828±1 479 (μg/mL)·h、CL(s)为0.393±0.017 L/(kg·h),Tmax为0.500±0.065 h,Cmax为1.424±0.156μg/mL、F为109.28%±6.25%。30 mg/kg bw剂量组 t1/2a为1.342±0.244 h、t1/2β为 20.052±1.236 h、t1/2Ka为 0.086±0.015h、AUC为57 575±6.760 (μg/mL)·h、CL(s)为0.527±0.068 L/(kg·h)、Tmax为0.437±0.039 h、Cmax为 3.343±0 512μg/mL、F为81.22%±9.54%。结果表明,绵羊静脉和皮下注射替米考星体内分布广,消除缓慢;皮下注射后在体内吸收迅速,达峰快,生物利用度高。     

碘醚柳胺脂质体定向剂在绵羊体内的药代动力学及组织残留量

应用碘醚柳胺脂质体定向剂 (包封率 58%)给绵羊单剂量皮下注射 ( 0 .3m g/ kg) ,用反相高效液相色谱法 ( RP- HPLC)测定了该药在绵羊体内不同时间的血浆药物浓度以及组织中的药物残留量。利用 3p87实用药代动力学软件分析 ,结果表明 ,该药的药代动力学符合一室模型 ,动力学方程为 :C =3.116 4( e- 0 .0 192 t- e- 1.5 15 5 t)。药代动力学参数为 :达峰时间 ( Tmax)为 ( 2 .8112± 0 .74 92 ) d,峰浓度 ( Cmax)为 ( 2 .874 2±0 .8716 ) mg/ L,生物半衰期 ( t1/2β)为 ( 36 .386 1± 3.0 385) d,曲线下面积 ( AU C)为 ( 14 3.5530± 4 7.2 354 )μg·m L- 1· d- 1。与皮下注射碘醚柳胺注射液 ( 3mg/ kg)相比 ,达峰浓度时间提前了 1.4 6 47d,半衰期延长了 16 .2 0 97d。碘醚柳胺在绵羊组织中的残留量 ,2 8d时肝脏中为 ( 2 3.0 331± 3.2 0 4 8) μg/ g。肾脏、肌肉和胆汁中一直检测不到药物。与皮下注射碘醚柳胺注射液相比 ,肝脏等富含巨噬细胞的脏器中药物含量明显增高 ,肾脏、肌肉中药物含量相对较低。本试验结果表明 ,碘醚柳胺脂质体定向剂优于碘醚柳胺注射液。     

Aspects of the Pharmacokinetics of Albendazole Sulphoxide in Sheep

The plasma disposition kinetics of albendazole sulphoxide (ABZSO), ((+)ABZSO and (–)ABZSO) and its sulphone metabolite (ABZSO₂) were investigated in adult sheep. Six Corriedale sheep received albendazole sulphoxide by intravenous injection at 5 mg/kg live weight. Jugular blood samples were taken serially for 72 h and the plasma was analysed by high-performance liquid chromatography (HPLC) for albendazole (ABZ), ABZ sulphoxide (ABZSO) and albendazole sulphone (ABZSO₂). Albendazole was not detected in the plasma at any time after the treatment, ABZSO and ABZSO₂ being the main metabolites detected between 10 min and 48 h after treatment. A biexponential plasma concentration versus time curve was observed for both ABZSO and ABZSO₂ following the intravenous treatment. The plasma AUC values for ABZSO and ABZSO₂ were 52.0 and 10.8 (g.h)/ml, respectively. The ABZSO₂ metabolite was measurable in plasma between 10 min and 48 h after administration of ABZSO, reaching a peak concentration of 0.38 g/ml at 7.7 h after treatment. Using a chiral phase-based HPLC method, a biexponential plasma concentration versus time curve was observed for both ABZSO enantiomers. The total body clearance was higher for the (–) than for the (+) enantiomer, the values being 270.6 and 147.75 (ml/h)/kg, respectively. The elimination half-life of the (–) enantiomer was shorter than that of the (+) enantiomer, the values being 4.31 and 8.33 h, respectively. The enantiomeric ratio (+)ABZSO/(–)ABZSO at t ₀ was close to unity. However, the ratio in the plasma increased with time.     

国产碘醚柳胺在绵羊体内的药代动力学及组织残留量的研究

给绵羊单剂量口服碘醚柳胺(7.5mg/kg),用HPLC法测定不同时间的血浆药物浓度。结果,碘醚柳胺在血浆中药物代谢动力学符合开放性二室模型,动力学方程为: C_t=208.586 8e~(-0.4756(t-0.5426)) 18.760 5e~(-0.0439(t-0.5426))-227.445e~(-0.5328(t-0.5426))口服碘醚柳胺后,达峰时间(Tmax)为3.698 9±0.197 4d;峰浓度(Cmax)为18.760 5±1.564 6μg/mL;消除半衰期(T(1/2)β)为15.800 6±0.445 7d;曲线下面积(Auc)为459.000 0±62.531 3μg·d/mL。碘醚柳胺在绵羊的肝、肾、胆汁、肌肉中的残留量:停药后28d分别为0.359 9、0.243 2、0.157 9、0.100 0μg/g;停药后50d,肝脏中的残留量为0.100 0μg/g,其它组织中均检测不到;停药后60d,各组织中均无残留。     

Pharmacokinetics of amikacin in plasma and selected body fluids of healthy horses after a single intravenous dose

Reasons for performing study: No studies have determined the pharmacokinetics of low‐dose amikacin in the mature horse. Objectives: To determine if a single i.v. dose of amikacin (10 mg/kg bwt) will reach therapeutic concentrations in plasma, synovial, peritoneal and interstitial fluid of mature horses (n = 6). Methods: Drug concentrations of amikacin were measured across time in mature horses (n = 6); plasma, synovial, peritoneal and interstitial fluid were collected after a single i.v. dose of amikacin (10 mg/kg bwt). Results: The mean ± s.d. of selected parameters were: extrapolated plasma concentration of amikacin at time zero 144 ± 21.8 µg/ml; extrapolated plasma concentration for the elimination phase 67.8 ± 7.44 µg/ml, area under the curve 139 ± 34.0 µg*h/ml, elimination half‐life 1.34 ± 0.408 h, total body clearance 1.25 ± 0.281 ml/min/kg bwt; and mean residence time (MRT) 1.81 ± 0.561 h. At 24 h, the plasma concentration of amikacin for all horses was below the minimum detectable concentration for the assay. Selected parameters in synovial and peritoneal fluid were maximum concentration (C_max) 19.7 ± 7.14 µg/ml and 21.4 ± 4.39 µg/ml and time to maximum concentration 65 ± 12.2 min and 115 ± 12.2 min, respectively. Amikacin in the interstitial fluid reached a mean peak concentration of 12.7 ± 5.34 µg/ml and after 24 h the mean concentration was 3.31 ± 1.69 µg/ml. Based on a minimal inhibitory concentration (MIC) of 4 µg/ml, the mean C_max : MIC ratio was 16.9 ± 1.80 in plasma, 4.95 ± 1.78 in synovial fluid, 5.36 ± 1.10 in peritoneal fluid and 3.18 ± 1.33 in interstitial fluid. Conclusions: Amikacin dosed at 10 mg/kg bwt i.v. once a day in mature horses is anticipated to be effective for treatment of infection caused by most Gram‐negative bacteria. Potential relevance: Low dose amikacin (10 mg/kg bwt) administered once a day in mature horses may be efficacious against susceptible microorganisms.     

Some Pharmacokinetic Parameters of Oxfendazole in Sheep

Soraci, A.L., Mestorino, N. and Errecalde, J.O., 1997. Some pharmacokinetic parameters of oxfendazole in sheep. Veterinary Research Communications, 21 (4), 283-287     

Pharmacokinetics of diclofenac in sheep following intravenous and intramuscular administration

OBJECTIVES: The aim of this work was to examine the pharmacokinetics of diclofenac (DCLF) in sheep after intravenous (IV) and intramuscular (IM) dosing. ANIMALS: Healthy male Najdi sheep. MATERIALS AND METHODS: Diclofenac (1 mg kg(-1)) was administered to ten clinically healthy-male Najdi sheep IV or IM (n = 5 each). Blood samples (5 mL) were collected and serum was separated for drug analysis by high-performance liquid chromatography with UV detection. Diclofenac pharmacokinetic parameters were determined by noncompartmental analysis. RESULTS: Diclofenac is quickly eliminated from sheep with a terminal T(1/2lambda) of 2-3 hours for both routes of administration. Total DCLF clearance after IV and IM administration was 87.86 +/- 24.10 and 85.69 +/- 40.76 mL kg(-1) hour(-1) respectively. The absolute bioavailability of IM DCLF appears to be approximately 100%. CONCLUSIONS AND CLINICAL RELEVANCE: The drug should be administered two to three times daily in sheep by IM or IV injection to maintain therapeutic concentrations. Additional studies are needed to evaluate the route of elimination of DCLF in sheep including metabolites formation and the significance of enterohepatic circulation.     

阿莫西林在藏系羊体内的药物动力学研究

为研究阿莫西林在藏系羊体内的药物动力学特征,了解阿莫西林在藏系羊体内的吸收、分布、转化及排泄规律,以期为牧区兽医临床用药提供依据。本试验选取8只成年藏系羊,阿莫西林口灌给药,不同时间点采集藏系羊血液,利用高效液相色谱法测定血浆中药物浓度。结果表明,阿莫西林经藏系羊口灌给药(15 mg/kg.B.W)后,其主要药动学参数为:t_(1/2α)为(0.773±0.097)h,t1/2ka为(0.156±0.021)h,t_(1/2β)为(3.787±0.973)h,AUC为(8.249±1.023)μg·h/m L,T_(max)为(0.497±0.036)h,C_(max)为(2.667±0.198)μg/m L。表明阿莫西林口灌给药后,在成年藏系羊体内吸收迅速,消除较快。     

Bioavailability and Pharmacokinetics of Sulphadiazine,N<Superscript>4</Superscript>-acetylsulphadiazine and Trimethoprim following Intravenous and Intramuscular Administration of a Sulphadiazine/Trimethoprim Combination in Sheep

The combination of sulphadiazine and trimethoprim is extensively used in farm animal species; however, there are no data concerning its pharmacokinetics after intramuscular administration in sheep. Twelve rams of the Chios breed were used to study the disposition of sulphadiazine, its metabolite N⁴-acetylsulphadiazine and trimethoprim after intravenous (i.v.) and intramuscular (i.m.) administration of a sulphadiazine/trimethoprim (5:1) combination in sheep. Sulphadiazine bioavailability (±SD) was 69.00%±10.51%. The half-life of the terminal phase (4.10±0.58 h afteri. v., and 4.03±0.31 h after i.m. administration) was significantly higher than the respective value for trimethoprim (0.59±0.19 h) afteri.v. administration. The maintenance of a constant plasma concentration ratio after i.v. administration was therefore impossible. The acetylation capacity in sheep, determined by the AUC ratio between N⁴-acetylsulphadiazine and the parent compound, sulphadiazine, was very low (less than 4%). The most remarkable finding of this study was that trimethoprim was not detected in sheep plasma after i.m. injection. In conclusion, according to the findings of the present study, following i.v. administration of the sulphadiazine/trimethoprim combination, trimethoprim can be considered as the limiting factor for any possible synergistic effect, and the i.m. route cannot be recommended in sheep.     

硫酸阿米卡星脂质体对小鼠的毒性研究

按750mg／kg体重给小鼠腹腔注射硫酸阿米卡星脂质体,7d后小鼠仍健活;再将80只小鼠随机分为4组,即140、70、35mg／kg和阴性对照组,连续20d腹腔注射硫酸阿米卡星脂质体后,进行血液学、血清生化学和组织病理学检查,结果与对照组无显著性差异。表明硫酸阿米卡星被制成脂质体制剂后,毒副作用大大降低,对动物无毒副作用。     

阿米卡星脂质体对猪肺疫的疗效试验

为研究阿米卡星脂质体的临床疗效,对10例被诊断为患猪肺疫（猪巴氏杆菌病）的仔猪进行了疗效试验。将患猪随机分为3组,空白对照组肌肉注射生理盐水;药物对照组肌肉注射阿米卡星,剂量为7．5mg／kg,每天用药2次,连用5d;试验药物组肌注阿米卡星脂质体,剂量为5．0mg／kg,每天用药1次,连用3d。结果表明,阿米卡星脂质体组治愈率和有效率分别为70．0％和76．0％,疗效显著高于药物对照组（P〈0．01）。     

Enhanced Plasma Availability of the Metabolites of Albendazole in Fasted Adult Sheep

Lifschitz, A., Virkel G., Mastromarino, M. and Lanusse C., 1997. Enhanced plasma availability of the metabolites of albendazole in fasted adult sheep. Veterinary Research Communications, 21 (3), 201-211The influence of fasting prior to treatment and of dosing rate on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO2) metabolites was studied in adult sheep grazing on pasture. A micronized suspension of ABZ was administered orally at either 7.5 mg/kg (group A) or 11.3 mg/kg (group C) to sheep fed ad libitum, and at 7.5 mg/kg to sheep subjected to a 24 h fasting period prior to treatment (group B). Blood samples were taken serially over 96 h after treatment, and the plasma was analysed for ABZ and its metabolites by high-performance liquid chromatography. ABZSO and ABZSO2 were recovered from the plasma. Fasting induced marked modifications in the pharmacokinetic behaviour of the ABZ metabolites in sheep. An extended absorption process, with a delayed peak concentration in the plasma, was observed for both metabolites in the fasted sheep. Significantly higher area under the curve (AUC) and peak plasma concentration (Cmax) values were obtained for both metabolites in the fasted animals compared to those fed ad libitum. Delayed elimination with prolonged detection in plasma was also observed in the fasted sheep. Treatment with ABZ at 7.5 mg/kg in the starved animals resulted in bioequivalence to the administration of the compound at a 50% higher dose rate (11.3 mg/kg) in the fed animals. It is suggested that fasting enhances ABZ dissolution and absorption by delaying its passage down the digestive tract.     

Pharmacokinetics of tulathromycin in fetal sheep and pregnant ewes

Macrolides are important antimicrobials frequently used in human and veterinary medicine in the treatment of pregnant women and pregnant livestock. They may be useful for the control of infectious ovine abortion, which has economic, animal health, and human health impacts. In this study, catheters were surgically placed in the fetal vasculature and amnion of pregnant ewes at 115 (±2) days of gestation. Ewes were given a single dose of 2.5 mg/kg tulathromycin subcutaneously, and drug concentrations were determined in fetal plasma, maternal plasma, and amniotic fluid at 4, 8, 12, 24, 36, 48, 72, 144, and 288 hr after drug administration. Pharmacokinetic parameters in maternal plasma were estimated using noncompartmental analysis and were similar to those previously reported in nonpregnant ewes. Tulathromycin was present in fetal plasma and amniotic fluid, indicating therapeutic potential for use against organisms in these compartments, though concentrations were lower than those in maternal plasma. Time‐course of drug concentrations in the fetus was quite different than that in the ewe, with plasma concentrations reaching a plateau at 4 hr and remaining at this concentration for the remainder of the sampling period (288 hr), raising questions about how tulathromycin may be transported into or metabolized and eliminated by the fetus.     

Pharmacokinetics of cefquinome after single and repeated subcutaneous administrations in sheep

The purpose of this study was to determine the pharmacokinetics of cefquinome (CFQ) following single and repeated subcutaneous (SC) administrations in sheep. Six clinically healthy, 1.5 ± 0.2 years sheep were used for the study. In pharmacokinetic study, the crossover design in three periods was performed. The withdrawal interval between the study periods was 15 days. In first period, CFQ (Cobactan, 2.5%) was administered by an intravenous (IV) bolus (3 sheep) and SC (3 sheep) injections at 2.5 mg/kg dose. In second period, the treatment administration was repeated via the opposite administration route. In third period, CFQ was administrated subcutaneously to each sheep (n = 6) at a dose of 2.5 mg/kg q. 24 hr for 5 days. Plasma concentrations of CFQ were measured using the HPLC‐UV method. Pharmacokinetic parameters were calculated using non‐compartmental methods. The elimination half‐life and mean residence time of CFQ after the single SC administration were longer than IV administration (p < 0.05). Bioavailability (F%) of CFQ following the single SC administration was 123.51 ± 11.54%. The area under the curve (AUC_0‐∞) and peak concentration following repeated doses (last dose) were higher than those observed after the first dose (p < 0.05). CFQ accumulated after repeated SC doses. CFQ can be given via SC at a dose of 2.5 mg/kg every 24 hr for the treatment of infections caused by susceptible pathogens, which minimum inhibitory concentration is ≤1.0 μg/ml in sheep.