硫酸安普霉素注射液中硫酸安普霉素含量的测定

本研究采用旋光法测定硫酸安普霉素注射液中硫酸安普霉素含量。结果表明：硫酸安普霉素在5～40mg/ml的浓度范围内呈良好的线性关系（r=0.99986,n=5）,回收率为99.6%,RSD：1.0%。说明能够简便、快速、重现性较好的测定硫酸安普霉素注射液（5ml：0.5g（500000IU））中硫酸安普霉素的含量,与药典规定的抗生素微生物检定法测定的结果有较好的可比性。适合药厂对该制剂中间产品的质量控制。     

硫酸安普霉素在猪体内的药代动力学研究

实验猪6头,单剂量(20mg/kg)静脉注射国产硫酸安普霉素,用微生物法测定血清药物浓度,研究其在猪体内的药代动力学.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0.05～3.00μg/ml范围呈良好线性关系(r=0.9965).猪静脉注射硫酸安普霉素血药浓度,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,t1/2c(0.75士0.21)h,t12β(3.019±0.67)h,CLB为(0.16士0.01)1/kg·h     

HPLC-ELSD法测定硫酸安普霉素含量的研究

建立了HPLC-ELSD法测定硫酸安普霉素、硫酸安普霉素可溶性粉和硫酸安普霉素预混剂中安普霉素的含量.采用XBridge C18柱(4.6×150 mm,5μm),以0.2 mol/L三氟乙酸-甲醇溶液(98:2)为流动相,柱温30℃,流速1.0 ml/min,雾化器加热级别为60%,漂移管温度为60℃,气体压力为35psi,增益为5.对照品在进样量为0.4-10μg范围内呈良好的线性关系(r=0.9997),安普霉素回收率为99.5%-102.7%.该方法简便、准确、快速,适合硫酸安普霉素及其制剂的质量控制.     

微生物浊度法测定硫酸安普霉素可溶性粉含量的研究方法

以金黄色葡萄球菌为试验茵,抗生素检定培养基Ⅲ号为试验用培养基,将硫酸安普霉素可溶性粉稀释成不同的浓度,寻找浓度的对数值与相对应的吸光度呈直线相关的线性范围。建立测定安普霉素含量的浊度法。安普霉素的浓度在2．9～7．2μg／ml之间,其浓度的对数值与相对应的吸光度呈直线相关,相关系数r为0．9962。经t检验安普霉素浓度的时数值与相对应的吸光度回归效果显著。所建立的浊度法平均回收率为100．10％,平均可信限率为3．05％,RSD为0．23％。管蝶法与浊度法所测得结果无显著差异。浊度法具有简便、精确、快速的特点,可用于安普霉素可溶性粉含量的测定。     

HPLC—ELSD法测定硫酸安普霉素含量的研究

建立了HPLC—ELSD法测定硫酸安普霉素、硫酸安普霉素可溶性粉和硫酸安普霉素预混剂中安普霉素的含量。采用XBridge C18柱（4．6×150mm,5μm）,以0．2mol／L三氟乙酸一甲醇溶液（98：2）为流动相,柱温30℃,流速1．0ml／min,雾化器加热级别为60％,漂移管温度为60℃,气体压力为35psi,增益为5。对照品在进样量为0．4-10μg范围内呈良好的线性关系（r=0．9997）,安普霉素回收率为99．5％-102．7％。该方法简便、准确、快速。适合硫酸安普霉素及其制剂的质量控制。     

好益特硫酸安普霉素可溶性粉

安普霉素（Apramycin）是美国于19世纪60年代研制出的具有广谱抗菌活性、畜禽专用的一类抗生素，亦称阿泊拉霉素．它是由黑暗链霉菌族菌产生的一种氨基环醇类抗生素，主要通过干扰原核生物核蛋白质的合成而抑制细菌的繁殖，对畜禽感染的革兰氏阴性菌有较强抗菌活性，特别是对其他抗生素耐药的大肠杆菌和沙门氏菌等有强抗菌作用，且不易产生耐药性，有广泛的市场前景和需求。安普霉素存活体内外可有力阻止蛋白质合成的易位阶段，该化合物常以硫酸盐的形式在兽医上应用。     

微生物浊度法测定硫酸安普霉素及制剂含量的试验研究

以金黄色葡萄球菌为供试菌,抗生素检定培养基Ⅲ号为试验用培养基.将硫酸安普霉素稀释成不同浓度,寻找浓度的对数值与相应的吸光度呈直线相关的线性范围,建立测定硫酸安普霉素及其制剂含量的浊度法.硫酸安普霉素的浓度在3.6～6.0 μ/mL之间,其浓度的对数值与相应的吸光度呈直线相关,相关系数r=0.9909.经t检验,硫酸安普霉素浓度的对数值与相对应的回归效果显著.所建立的浊度法平均回收率为100.73%,平均可信限率为2.94%,RSD为0.31%.     

微生物浊度法测硫酸安普霉素及其制剂含量的研究

以抗生素检定培养基Ⅲ号为试验用培养基,金黄色葡萄球菌为试验菌,将硫酸安普霉素稀释成不同的浓度,寻找其呈直线相关的线性范围,并对所建立的浊度法进行准确度、精密度、专属性、浊度法与管碟法比较等验证。结果表明:硫酸安普霉素的浓度在2.9～7.2u/ml之间时,其浓度的对数值与相对应的吸光度具有良好的线性关系,相关系数:R2=0.9988。硫酸安普霉素所建立的微生物浊度法平均回收率及平均可信限率为100.00%和1.88%。浊度法与管碟法所测结果无显著差异。浊度法具有简便、精确、快速的特点,可用于硫酸安普霉素及其制剂含量的测定。     

高效液相色谱法测定硫酸安普霉素有关物质

建立了硫酸安普霉素有关物质测定的高效液相色谱法。硫酸安普霉素有关物质经磺酸基键合硅胶柱分离,茚三酮溶液衍生后,568 nm处测定。结果显示,测得的硫酸安普毒素8种有关物质得到良好分离。对硫酸安普霉素及其制剂测定结果表明,该方法适合硫酸安普霉素有关物质的测定。     

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.     

Tissue damage and concentration at the injection site after intramuscular injection of chemotherapeutics and vehicles in pigs.

Intramuscular injection sites were examined for macroscopical and microscopical changes and for residues of drugs six and 30 days after injection of chemotherapeutic preparations or vehicles in swine. The chemotherapeutic preparations contained sulphonamide and/or trimethoprim. All the chemotherapeutic preparations and the vehicles except physiological saline and sterile water caused macroscopical and microscopical changes, mainly appearing as areas of necrotic muscle tissue six days after the injection and as scar tissue 30 days after the injection. Residues of drugs were found at nearly all the injection sites six days after the injection, while 30 days after the injection only residues of sulphonamides were detectable in nearly half of the injection sites.     

Serum alpha-tocopherol concentration in sheep after intramuscular injection of DL-alpha-tocopherol.

Forty-three crossbred wethers weighing 35 to 60 kg were used to investigate the effect of a single i.m. injection of DL-alpha-tocopherol (DL-alpha-ol). Animals were offered 1 kg/d of a basal diet containing 25 ppm of vitamin E. Lambs were randomly assigned to one of five DL-alpha-ol injection treatments as follows: 1) control (placebo, 0 IU), 2) 125 IU, 3) 250 IU, 4) 500 IU, or 5) 1,000 IU. Blood samples were taken via jugular venipuncture on d 1 before treatment administration and thereafter at designated intervals up to 360 h postinjection. The i.m. injections of DL-alpha-ol irrespective of dose increased serum alpha-tocopherol. Results showed a dose x time interaction (P less than .0001) across all treatments. Serum alpha-tocopherol increased rapidly to maximum concentration during the first 8 to 12 h for all non-zero treatments, followed by a rapid decline to pretreatment values. The mean serum alpha-tocopherol concentration at 0 h was .69 microgram/mL. Estimated peak serum alpha-tocopherol concentrations +/- SE were 6.68 +/- 1.04, 9.62 +/- 1.04, 21.66 +/- 2.37, and 50.75 +/- 7.05 micrograms/mL for Treatments 2 through 5, respectively. Results showed a quadratic dose effect (P less than .0003) on maximum response with apparently no effect on time taken to reach this peak. There was also a quadratic dose effect (P less than .0001) on the area under the concentration-time curve. The time taken for serum alpha-tocopherol to return to pretreatment levels increased with dose (56, 64, 67, and 74 h, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of butorphanol in horses after intramuscular injection

A two-way cross-over study of the pharmacokinetics of butorphanol after intravenous and intramuscular administration at 0.08 mg/kg in six adult horses was performed. Heparinized venous blood samples were obtained prior to drug administration and at 10, 20, 30, 45, 60, 120, 180, 240, and 360 min after IV injection. Samples were obtained at the same time points and at 6 h and 12 h after IM injection. Physical examination parameters were recorded at each time point. Plasma butorphanol concentrations were determined by high performance liquid chromatography. No significant differences in any physical parameters were observed after butorphanol administration except for an increase in respiratory rate at 60 and 180 min after IV administration. Absorption of butorphanol after IM administration was very rapid (half life of absorption of 6 min) but systemic availability after IM injection was low (37%). Terminal half-life after IV administration was much longer than half-life after IM administration (0.57 h and 7.7 h, respectively). This difference was attributed to detection of a deep compartment after IV administration that was not detectable after IM administration. To maintain targeted plasma butorphanol concentrations above 10 ng/mL, administration of 0.08 mg/kg IM every 3 h may be necessary.     

肌肉注射盐酸头孢噻呋混悬注射液对猪安全性试验

头孢噻呋(ceftiofur)是第一个畜禽专用的第3代头孢菌素类抗生素,具有抗菌谱广、抗菌活性强、对胃酸和β-内酰胺酶较稳定、过敏反应少、毒性小、在动物体内残留低的特点[1].国内外已批准的制剂有注射用头孢噻呋钠和盐酸头孢噻呋注射液,用于肉牛、奶牛、马、羊、猪呼吸道病和1日龄鸡细菌性感染的防治[2].     

Distribution of neomycin in bull calves after intramuscular injection

Neomycin sulfate was injected intramuscularly in calves. Blood and tissue samples were taken at zero, one, two, four, six, eight and 24 hours after administration. The tissues with high levels (greater than 10 μg/g) of drug at the one hour period were kidney cortex and medulla, urine, blood serum and the injection site. By 24 hours after administration only the kidney cortex and urine had high levels of neomycin. The drug could not be detected in any brain tissues and very small amounts (less than 1 μg/g) were present in the bile, thymus and vitreous humor. Levels greater than 5 μg/g were present in lung tissues for less than four hours but were greater than 2 μg/g for more than 24 hours.

The mean level in the injection site was greater than 700 μg/g at one hour but only trace amounts were found at 24 hours.

On the basis of the tissue drug concentration intramuscularly administered neomycin was suggested as therapeutically useful for respiratory and urinary tract infections caused by susceptible bacteria.

     

Comparison of plasma pharmacokinetics and bioavailability of ceftiofur sodium and ceftiofur hydrochloride in pigs after a single intramuscular injection

Ceftiofur sodium, a broad-spectrum cephalosporin, is active against gram-positive and gram-negative pathogens of veterinary importance. Two studies were designed to compare the intramuscular bioavailability of the current sodium salt and the new hydrochloride salt in pigs at doses of either 3 mg or 5 mg ceftiofur equivalents (CE)/kg body weight. Twenty-six healthy young pigs were selected for these two-period, two-treatment crossover studies, 12 for the 3 mg/kg study and 14 for the 5 mg/kg study. Each animal received one intramuscular (i.m.) injection of ceftiofur sodium and one i.m. injection of ceftiofur hydrochloride with a 14-day washout period between the two treatments. Blood samples were collected serially for up to 96 h postinjection. Plasma samples were then analysed using a validated assay that measures ceftiofur and all desfuroylceftiofur-related metabolites by high-performance liquid chromatography. In the 3 mg/kg dosage study, average maximum plasma concentration (C(max)) after administration of ceftiofur sodium was 15.8+/-3.40 microg/mL at 0.4-4 h after injection. After administration of ceftiofur hydrochloride, the C(max) was 11.8+/-1.67 microg/mL at 1-4 h after injection. Concentrations of ceftiofur and metabolites 72 h after the injection were 0.392+/-0.162 microg/mL for ceftiofur hydrochloride and 0.270+/-0.118 microg/mL for ceftiofur sodium. The mean area under the curve (AUC), from time 0 to the limit of quantitation (AUC(O-LOQ)) after ceftiofur hydrochloride administration, was 216+/-28.0 microg x h/mL, compared to 169+/-45.4 microg x h/mL after ceftiofur sodium administration. The calculated time during which plasma concentrations remained above 0.02 microg/mL (t(>0.2)) was 85.3+/-10.6 h for ceftiofur sodium and 77.2+/-10.7 h for ceftiofur hydrochloride. In the 5 mg/kg dosage study, C(max) after administration of ceftiofur sodium was 28.3+/-4.45 microg/mL at 0.33-2 h after injection. After administration of ceftiofur hydrochloride, the C(max) was 29.7+/-6.72 microg/mL at 0.66-2 h after injection. Concentrations of ceftiofur and metabolites 96 h after the injection were 0.274+/-0.0550 microg/mL for ceftiofur hydrochloride and 0.224+/-0.0350 microg/mL for ceftiofur sodium. The mean AUC(O-LOQ) after ceftiofur hydrochloride administration was 382+/-89.8 microg x h/mL compared to 302+/-54.4 microg x h/mL after ceftiofur sodium administration. The t(>0.2) was 78.9+/-9.65 h for ceftiofur sodium and 94.2+/-8.64 h for ceftiofur hydrochloride. Based on the similarity of the pharmacokinetic parameters of the sodium and hydrochloride formulations of ceftiofur, similar therapeutic efficacy can be inferred for the two products.     

肌注PHA对犬血清中补体C3、C4的影响

对各犬只肌注PHA,通过测定不同时期血清中补体C3,C4的浓度,以判定PHA对补体的影响作用。把PHA分成4个剂量组:低剂量组(0.05 mg/kg)、中剂量组(0.10 mg/kg)、高剂量组(0.20 mg/kg)和对照组(相同剂量的生理盐水)。在注射前和注射后的7 d、14 d对各组实验犬只进行采血分析,测定其血清中补体的含量,并进行统计学分析。结果显示,不同剂量的PHA对犬只的补体系统刺激作用不同,其中中剂量组可以极大地提高机体的补体水平,并保持一定时间的高水平,而低剂量组和高剂量组的差异不显著。