HPLC法测定硫酸头孢喹肟冻干粉针中硫酸头孢喹肟含量

建立高效液相色谱法(HPLC法)测定硫酸头孢喹肟冻干粉针中硫酸头孢喹肟的含量。色谱条件为色谱柱Kromasil C18柱(250 mm×4.6 mm,5μm),以高氯酸钠-磷酸-三乙胺缓冲液(pH3.6):乙腈(体积比90∶10)为流动相,流速为0.8 mL/min,紫外检测波长为254 nm。结果表明,硫酸头孢喹肟在0.05~25μg/mL范围内呈良好的线性关系,r=0.99 96,平均回收率为100.34%(n=9),RSD为1.34%。该方法简便快速,结果准确可靠,可用于硫酸头孢喹肟冻干粉的质量控制研究。     

硫酸头孢喹肟在鸭体内的药动学及生物利用度研究

试验将20只2月龄健康番鸭,随机分为2组,每组10只,雌雄各半,分别进行静脉注射和口服硫酸头孢喹肟给药的药动学研究。静脉注射和口服的给药剂量分别为10和20 mg/kg。以反相HPLC测定血浆中硫酸头孢喹肟的浓度,血药浓度—时间数据用3P97药动学程序软件处理。鸭单剂量静脉注射给药后,血药浓度—时间数据符合无吸收二室开放模型,其主要动力学参数分别为:V（c）,（1.146±0.02） L/kg;t_1/2α,（0.290±0.02）h;t_1/2β,（1.691±0.15）h;AUC （6.635±0.18）（mg·h）/L;CL（s）,（1.508±0.04）L/（kg·h）。鸭口服硫酸头孢喹肟的血药浓度—时间数据符合一级吸收一室开放模型,主要动力学参数分别为:t_1/2（ka）,（0.45±0.05）h;t_1/2（ke）,（0.96±0.29）h;T_（peak）,（0.91±0.09）h;C_（max）,（3.14±0.64）mg/L;AUC,（8.29±1.26）（mg·h）/L;F,（62.55±0.10）%。硫酸头孢喹肟在体内的药动学特征表现为吸收迅速、分布广泛、消除迅速。但口服给药在鸭体内生物利用度低,可能由于硫酸头孢喹肟的脂溶性低,其在消化道吸收率低所致。但8 h内能保持有效血药浓度范围（（0.14±0.03）~（3.14±0.64）μg/mL）,可抑制鸭疫里默氏杆菌及其他细菌感染。     

硫酸头孢喹肟注射液在猪体内的生物等效性研究

为研究国产和进口硫酸头孢喹肟注射液(7.5%)在猪体内的药代动力学特征和生物等效性,采用双处理、双周期随机交叉试验设计,将20头健康三元杂交猪随机分成2组,按3mg/kg体重分别单剂量肌内注射受试制剂和参比制剂。采用超高效液相色谱-串联质谱法测定血浆中头孢喹肟的浓度,利用Win Nonlin6.3软件计算主要药动学参数,并评价两种制剂的生物等效性。结果显示,受试制剂和参比制剂的Tmax分别为2.30±0.73h和2.25±0.55h;Cmax分别为2.37±0.34μg/mL和2.45±0.36μg/mL;AUC0-t分别为26.38±2.30μg·h·mL^-1和24.86±2.19μg·h·mL^-1;AUC0-∞分别为26.74±2.34μg·h·mL^-1和25.07±2.20μg·h·mL^-1。硫酸头孢喹肟注射液受试制剂和参比制剂的AUC0-t、AUC0-∞、Cmax、Tmax均无显著性差异(P>0.05)。双单侧t检验结果显示两种制剂生物等效,临床上可相互替代。该试验可为兽医临床合理用药提供参考。     

硫酸头孢喹肟在鸡体内的药动学和生物利用度研究

为了解硫酸头孢喹肟口服和静注给药在鸡体内的动力学特征,用高效液相色谱法测定鸡血浆中的药物质量浓度,所得硫酸头孢喹肟血药浓度数据用3p97计算机软件处理。结果显示:硫酸头孢喹肟以每公斤体重10 mg单剂量静注给药,药物浓度-时间数据经药动学程序拟合符合无吸收二室开放动力学模型,主要药动学参数分别为:中央室分布容积V(c)(1.16±0.02)L·kg-1,分布半衰期T1/2α(0.29±0.03)h,消除半衰期T1/2β(1.69±0.24)h,曲线下面积AUC(6.57±0.18)mg·L-1·h,清除率CL/f(s)(1.53±0.04)mg·L-1·h。硫酸头孢喹肟以每公斤体重20 mg口服给药的血药浓度时间数据,符合一级吸收一室开放模型,主要动力学参数:吸收半衰期T1/2 ka(0.52±0.04)h,消除半衰期T1/2 ke(0.88±0.05)h,峰时Tmax(1.07±0.02)h,最高血药浓度Cmax(3.63±0.25)μg·mL-1,曲线下面积AUC(9.84±0.68)mg·L-1·h,表观分布容积V/f(c)(3.85±0.30)L·kg-1·h-1,生物利用度F(74.9±0.06)%。结果表明:硫酸头孢喹肟静注给药能迅速从血液分布进入组织中,在体液中具有良好的渗透和分布性能,体内分布广泛,能迅速从血液中消除。口服给药吸收迅速,达峰时间短。口服给药在鸡体内生物利用度稍低,可能由于硫酸头孢喹肟的脂溶性低,其在消化道吸收率低所致。但在8 h内能保持有效血药浓度范围(0.09⁵.74μg·mL-1),可以有效控制常见细菌感染。     

硫酸头孢喹肟乳房注入剂在牛奶中的药代动力学研究

选取8头健康黑白花奶牛,每头牛随机选择两个乳区,以每个乳区1支(8g:75mg/支)的剂量进行单次乳房灌注给予硫酸头孢喹肟乳房注入剂。采用超高效液相色谱-串联质谱(UPLC-MS/MS)方法检测乳中头孢喹肟的浓度。结果表明,该制剂采用单次乳房灌注给药后,乳中药物能发挥较好抑菌效果的时间约为24～30小时,因此建议该制剂治疗奶牛临床型乳房炎的用药方案为：1支(8g:75mg)/(乳区.次),每天给药1次。     

硫酸头孢喹肟注射液的制备工艺研究

通过对硫酸头孢喹肟注射液的辅料及分散工艺进行研究,确定了硫酸头孢喹肟注射液的制备工艺。选择油酸乙酯为载体并对其相容性进行了研究;确定了2．0％的硬脂酸铝作为助悬剂;确定了1．0％的卵磷脂作为表面活性剂;确定了高剪切分散后过高压均质机均质作为分散工艺,最终确定了硫酸头孢喹肟注射液的制备工艺。并将产品按照质量标准进行检测,结果符合规定。     

猪肌肉注射硫酸头孢喹肟注射液的安全性试验

本试验对硫酸头孢喹肟进行了大、小鼠经口的急性毒性试验和猪肌肉注射硫酸头孢喹肟的安全性研究。选用SD大鼠和ICR小鼠各30只,其经口LD50均大于5 000 mg/kg。随机挑选健康猪12头,分为3组,按2 mg/kg、6 mg/kg和10 mg/kg剂量颈部肌肉注射硫酸头孢喹肟注射液,每日1次,连续5 d。对其给药前后的血常规和血液生化指标分析比较,并每天观察给药后动物临床表现。试验结果显示:硫酸头孢喹肟注射液在2~10 mg/kg剂量范围对猪血液生理生化指标无显著影响(P>0.05),所有动物给药后采食、行动、呼吸和排泄均未见异常,注射部位未见肿胀结块等现象,除10 mg/kg剂量组动物出现短时疼痛反应外,未观察到任何不良反应。     

硫酸头孢喹肟注射液在猪体内的药代动力学及生物等效性研究

为了研究硫酸头孢喹肟注射液在猪体内的药代动力学及生物等效性,将10头健康猪随机分成两组,按2 mg/kg体重肌肉注射两种硫酸头孢喹肟注射液,采用高效液相色谱法测定血浆中硫酸头孢喹肟的浓度,计算主要药代动力学参数,评价两制剂的生物等效性.肌肉注射两种硫酸头孢喹肟注射液后两组的消除半衰期(T1/2β)、达峰浓度(Cmax)、曲线下面积(AUC)等参数差异不显著(P＞0.05).采用双单侧t检验进行判断,受试组AUC 90％置信区间为108.2％ ～ 115.3％,在对照组均值的80％～120％范围内;Cmax90％置信区间为91.9％～115.3％,在对照组均值的70％ ～130％范围内.两种产品在猪体内具有生物等效性和类似的药代动力学,为临床给药方案的制定和临床合理用药提供了参考.     

关于硫酸头孢喹肟在猪、牛体内的药理学研究综述

头孢喹肟具有很广的抗菌谱,很强的抗菌活性,可以迅速吸收,具有安全,高效的特点,对由耐药金葡菌等革兰氏阳性菌及一些革兰氏阴性杆菌引起的严重感染,如肺部感染、尿路感染、败血症、脑膜炎、心内膜炎、子宫内膜炎等具有显著的疗效,未来有望广泛应用于猪、牛的临床治疗。头孢喹肟,又称头胞喹诺,是动物用第四代头胞类药物。本文主要综述硫酸头孢喹肟在猪、牛体内的药理学最新研究进展,包括硫酸头孢喹肟的药效学研究、药动学研究、毒理学研究、残留消除、临床应用五方面内容。以期为临床应用提供借鉴。     

高效液相色谱法测定动物性食品中头孢喹肟残留量

为建立同时适用于猪、牛的肌肉、脂肪、肝脏、肾脏及牛奶样品中头孢喹肟的残留检测方法,以磷酸缓冲液-乙腈混合溶液为提取液对试样中的头孢喹肟进行提取,并使用HLB固相萃取柱净化,建立了上述样品中头孢喹肟残留检测的高效液相色谱方法。经测定,该方法对肌肉、脂肪组织中头孢喹肟的定量限为25μg/kg;对肝脏、肾脏组织中头孢喹肟的定量限为50μg/kg;对牛奶中头孢喹肟的定量限为10μg/kg。该方法在以上各样品中的回收率均在60%～100%范围内。稳定性检验结果显示,样品中添加头孢喹肟,其含量稳定性可维持7 d。该方法准确可靠、可操作性强,能满足实际工作的需求。     

Pharmacokinetics of a single intramuscular injection of cefquinome in buffalo calves

The objective of this study was to investigate the pharmacokinetics of cefquinome following single intramuscular (IM) administration in six healthy male buffalo calves. Cefquinome was administered intramuscularly (2 mg/kg bodyweight) and blood samples were collected prior to drug administration and up to 24 hr after injection. No adverse effects or changes were observed after the IM injection of cefquinome. Plasma concentrations of cefquinome were determined by high‐performance liquid chromatography. The disposition of plasma cefquinome is characterized by a mono‐compartmental open model. The pharmacokinetic parameters after IM administration (mean ± SE) were C_max 6.93 ± 0.58 μg/ml, T_max 0.5 hr, t_½kα 0.16 ± 0.05 hr, t_½β 3.73 ± 0.10 hr, and AUC 28.40 ± 1.30 μg hr/ml after IM administration. A dosage regimen of 2 mg/kg bodyweight at 24‐hr interval following IM injection of cefquinome would maintain the plasma levels required to be effective against the bacterial pathogens with MIC values ≤0.39 μg/ml. The suggested dosage regimen of cefquinome has to be validated in the disease models before recommending for clinical use in buffalo calves.     

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.     

Pharmacokinetics and bioavailability of cefquinome and ceftriaxone in premature calves

The aim of this study was to evaluate the pharmacokinetics and bioavailability of cefquinome (CFQ) and ceftriaxone (CTX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. Using a parallel design, 24 premature calves were randomly divided into the two antibiotic groups. Each of the six animals in the first group received CFQ (2 mg/kg) through IV or IM administration. The second group received CTX (20 mg/kg) via the same administration route. Plasma concentrations of the drugs were analyzed by high‐performance liquid chromatography and noncompartmental methods. Mean pharmacokinetic parameters of CFQ and CTX following IV administration were as follows: elimination half‐life (t_1/2λz) 1.85 and 3.31 hr, area under the plasma concentration–time curve (AUC_0–∞) 15.74 and 174 hr * μg/ml, volume of distribution at steady‐state 0.37 and 0.45 L/kg, and total body clearance 0.13 and 0.12 L hr^?1 kg^?1, respectively. Mean pharmacokinetic parameters of CFQ and CTX after IM injection were as follows: peak concentration 4.56 and 25.04 μg/ml, time to reach peak concentration 1 and 1.5 hr, t_1/2λz 4.74 and 3.62 hr, and AUC_0–∞ 22.75 and 147 hr * μg/ml, respectively. The bioavailability of CFQ and CTX after IM injection was 141% and 79%, respectively. IM administration of CFQ (2 mg/kg) and CTX (20 mg/kg) can be recommended at 12‐hr interval for treating infections caused by susceptible bacteria, with minimum inhibitory concentration values of ≤0.5 and ≤4 μg/ml, respectively, in premature calves. However, further research is indicated to assess the pharmacokinetic parameters following multiple doses of the drug in premature calves.     

Pharmacokinetics of ceftiofur sodium in cats following a single intravenous and subcutaneous injection

Ceftiofur, a third‐generation cephalosporin antibiotic, is being extensively used by pet doctors in China. In the current study, the detection method was developed for ceftiofur and its metabolites, desfuroylceftiofur (DCE) and desfuroylceftiofur conjugates (DCEC), in feline plasma. Then, the pharmacokinetics studies were performed following one single intravenous and subcutaneous injection of ceftiofur sodium in cats both at 5 mg/kg body weight (BW) (calculated as pure ceftiofur). Ceftiofur, DCE, and DCEC were extracted from plasma samples, then derivatized and further quantified by high‐performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetics parameters. The terminal half‐life (t_1/2λz) was calculated as 11.29 ± 1.09 and 10.69 ± 1.31 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady‐state (V_SS) were determined as 14.14 ± 1.09 ml hr^‐1 kg^‐1 and 241.71 ± 22.40 ml/kg, respectively. After subcutaneous injection, the peak concentration (C_max; 14.99 ± 2.29 μg/ml) was observed at 4.17 ± 0.41 hr, and the absorption half‐life (t_1/2ka) and absolute bioavailability (F) were calculated as 2.83 ± 0.46 hr and 82.95%±9.59%, respectively. The pharmacokinetic profiles of ceftiofur sodium and its related metabolites demonstrated their relatively slow, however, good absorption after subcutaneous administration, poor distribution, and slow elimination in cats. Based on the time of drug concentration above the minimum inhibitory concentration (MIC) (T>MIC) calculated in the current study, an intravenous or subcutaneous dose at 5 mg/kg BW of ceftiofur sodium once daily is predicted to be effective for treating feline bacteria with a MIC value of ≤4.0 μg/ml.     

氟苯尼考纳米晶在鸡体内的药动学

氟苯尼考(florfenicol, FFC)是新型动物广谱抗菌剂,抗菌效果好,广泛应用于牛、羊、猪、水产及禽类等动物细菌性疾病的防制。本试验旨在研究FFC和氟苯尼考纳米晶(florfenicol nanocrystal, FFC-NC)在鸡体内的生物利用度。采用交叉试验法,鸡用药后,在不同时间点翅下静脉采血,利用高效液相色谱法(high performance liquid chromatography, HPLC)测定血浆中FFC含量。结果显示,此试验所建立的HPLC色谱图基线平稳,血浆峰与FFC峰完全分离。回收率和精密度均符合测定要求,重复性好,适用于鸡血浆FFC含量测定。药动学参数结果显示,与FFC组相比,FFC-NC组的达峰时间t_max为(0.875±0.137) h,峰时缩短,药时曲线下面积AUC₍(0-∞))和峰浓度C_max分别为(23.957±2.338) mg/(L·h)和(8.249±0.713) mg/L,FFC-NC组的相对生物利用度是FFC组的3.6倍。结果表明,FFC-NC的药动学特征较FFC均...     

Pharmacokinetics of ceftiofur sodium in Peekapoo dogs following a single intravenous and subcutaneous injection

The present study aimed to determine the pharmacokinetic profiles of ceftiofur (as measured by ceftiofur and its active metabolites concentrations) in a small-size dog breed, Peekapoo, following a single intravenous or subcutaneous injection of ceftiofur sodium. The study population comprised of five clinically healthy Peekapoo dogs with an average body weight (BW) of 3.4 kg. Each dog received either intravenous or subcutaneous injection, both at 5 mg/kg BW (calculated as pure ceftiofur). Plasma samples were collected at different time points after the administration. Ceftiofur and its active metabolites were extracted from plasma samples, derivatized, and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetic parameters. The terminal half-life (t_1/2λz) was calculated as 7.40 ± 0.79 and 7.91 ± 1.53 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (V_SS) were determined as 39.91 ± 4.04 ml hr⁻¹ kg⁻¹ and 345.71 ± 28.66 ml/kg, respectively. After subcutaneous injection, the peak concentration (C_max; 10.50 ± 0.22 μg/ml) was observed at 3.2 ± 1.1 hr, and the absorption half-life (t_1/2ka) and absolute bioavailability (F) were calculated as 0.74 ± 0.23 hr and 91.70%±7.34%, respectively. The pharmacokinetic profiles of ceftiofur and its related metabolites demonstrated their quick and excellent absorption after subcutaneous administration, in addition to poor distribution and slow elimination in Peekapoo dogs. Based on the time of concentration above minimum inhibitory concentration (T > MIC) values calculated here, an intravenous or subcutaneous dose at 5 mg/kg of ceftiofur sodium once every 12 hr is predicted to be effective for treating canine bacteria with a MIC value of ≤4.0 μg/ml.     

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。     

Pharmacokinetics of cefquinome in red‐eared slider turtles (Trachemys scripta elegans) after single intravenous and intramuscular injections

The purpose of this study was to evaluate the pharmacokinetics of cefquinome (CFQ ) following single intravenous (IV ) or intramuscular (IM ) injections of 2 mg/kg body weight in red‐eared slider turtles. Plasma concentrations of CFQ were determined by high‐performance liquid chromatography and analyzed using noncompartmental methods. The pharmacokinetic parameters following IV injection were as follows: elimination half‐life (t _1/2λz) 21.73 ± 4.95 hr, volume of distribution at steady‐state (V _dss) 0.37 ± 0.11 L/kg, area under the plasma concentration–time curve (AUC _0–∞) 163 ± 32 μg hr^?1 ml^?1, and total body clearance (Cl_T) 12.66 ± 2.51 ml hr^?1 kg^?1. The pharmacokinetic parameters after IM injection were as follows: peak plasma concentration (C _max) 3.94 ± 0.84 μg/ml, time to peak concentration (T _max) 3 hr, t _1/2λz 26.90 ± 4.33 hr, and AUC _0–∞ 145 ± 48 μg hr^?1 ml^?1. The bioavailability after IM injection was 88%. Data suggest that CFQ has a favorable pharmacokinetic profile with a long half‐life and a high bioavailability in red‐eared slider turtles. Further studies are needed to establish a multiple dosage regimen and evaluate clinical efficacy.