酒石酸乙酰异戊酰泰乐菌素在猪体内的药代动力学研究

健康猪口服酒石酸乙酰异戊酰泰乐菌素(AIV),不同时间点采血,高效液相色谱法测定血药浓度,残数法拟合药时曲线,计算药动学参数.结果表明,6头猪口服AIV(20mg/kg体重)后,其药动学表现有吸收因素二室模型特征.最佳药时曲线方程为:C=0.654·e-2.0593·t+0.981 3·e-3.0973·t-1.635 3·e-63.3197·t;吸收半衰期(t1/2Ka)为0.014 9±0.012 7 d,消除半衰期(t1/2ke)为0.1138±0.055 5 d,药时曲线下面积(AUC)为0.604 5±0.068 3(μg/mL)·d.表明酒石酸乙酰异戊酰泰乐菌素在猪体内吸收迅速,消除相对较慢.     

泰乐菌素 酒石酸泰乐菌素 磷酸泰乐菌素

泰乐菌素　　泰乐菌素 (Tylosin)由链霉菌 (Streptomycesfradiae)的类似菌株培养液中取得。按干燥品计算 ,每lmg效价不得少于 83 0泰乐菌素单位。【性状】　白色至浅黄色粉末。在甲醇中易溶 ,在乙醇、丙酮、氯仿中溶解 ,在水中微溶 ,在己烷中几乎不溶。其盐类易溶于水 ,水溶液在 2 5℃、pH值为 5 .5～ 7.5中可保存 3个月不减效。【药理】药效学　抗菌作用机理和抗菌谱与红霉素相似。对革兰氏阳性菌和一些阴性茵有效。敏感菌有金黄葡萄球菌、化脓链球菌、肺炎链球菌、化脓棒状杆菌等。对支原体属特别有效 ,是大环内酯类中抗支原体作用最强…     

酒石酸泰乐菌素对鸡细胞免疫应答的影响

许多报道都认为抗生素对白细胞功能 ,尤其是对多形核白细胞和淋巴细胞的功能有抑制作用。然而 ,最近发现大环内酯类的红霉素在体内外对多形核白细胞和巨噬细胞的趋化性、吞噬能力、白细胞增殖 ,超氧化物的产生白细胞介素 - 1(IL- 1)和肿瘤坏死因子 (TNF)活性 ,刀豆蛋白 A(Con A)诱导的母细胞化程度及自然杀伤细胞活性等功能有促进作用。收稿日期 :2 0 0 0 -0 6-2 0　　这就揭示了大环内酯类抗生素酒石酸泰乐菌素(可溶性泰农 )也有与红霉素相类似的作用 ,但很少有关于泰乐菌素对鸡细胞免疫功能影响的报道。本研究中采用给肉鸡口服泰乐菌…     

HPLC法测定酒石酸泰乐菌素及利巴韦林可溶性粉含量

采用CLC—ODSC18色谱柱,乙腈—0.05mol/L磷酸二氢钾(20∶80)为流动相,检测波长为207nm,HPLC外标法测定酒石酸泰乐菌素、利巴韦林可溶性粉中酒石酸泰乐菌素和利巴韦林含量,该法分离度大,专属性强,重复性好。     

紫外分光光度法测定酒石酸泰乐菌素及其可溶性粉含量

采用紫外分光光度法测定酒石酸泰乐菌素原料药及其可溶性粉含量。结果表明，泰乐菌素在5-40μg／mL范围内呈良好的线性关系（r=0．9996，n=5）。与法定的抗生素法检测结果无差异。     

HPLC法测定复方制剂中的酒石酸泰乐菌素

采用Kromasil C18色谱柱,甲醇-水(80:20)为流动相,检测波长为290nm,以HPLC外标法测定复方制剂中酒石酸泰乐菌素的含量。该法分离度大,被测组分的线性关系良好(r=0.9999),平均回收率100.0%,重复进样相对标准偏差0.16%。     

高效液相色谱法测定酒石酸泰乐菌素有关物质的研究

依据欧洲药典讨论稿中酒石酸泰乐菌素有关物质的检测方法,在280 nm波长处,以pH 5.5的磷酸盐缓冲溶液-乙腈-水(10∶27.5∶62.5,V/V)为A流动相,以pH 5.5的磷酸盐缓冲溶液-水-乙腈(10∶40∶50,V/V)为B流动相进行梯度洗脱,并对专属性、准确度、精密度、检测限和定量限、线性和范围、耐用性、及溶液稳定性进行考察。结果显示,杂质A、N、O、R、S峰峰面积与其对应浓度呈线性关系,其相关系数r均大于0.999,各项考察指标均符合要求。结果证明该分析方法能科学、合理的分析、控制酒石酸泰乐菌素有关物质,可以持续、准确地反映酒石酸泰乐菌素的特性。     

酒石酸泰乐菌素在鸡猪山羊体内的药动学规律及肌肉药残量研究

酒石酸泰乐菌素以25mg/kg、7.5mg/kg、10mg/kg给各6只（头）本地鸡、猪、山羊一次肌注,在不同时间分别采血制样,在UV290nm处测定光密度与各自标准曲线对照,获得不同时间血药浓度,试验数据用“WTS.IM.BAS”药动学软件计算机自动求算拟合,血药浓度经时过程均符合一级吸收一室开放模型,其主要参数见表2。结果表明：其在鸡的吸收速度较快,吸收较完全,消除较慢,猪次之,山羊再次之;故在鸡维持有效血药浓度时间较长,疗效较好,但每日给药一次均难达治疗目的。取不同时间的三种动物各4只（头）肌肉制样测定,并与各自标准曲线对照。结果表明：24h肌肉中残留药物浓度均低于0.05μg/g,休药48h肉品即较安全。     

酒石酸泰乐菌素残留蛋白质检验方法的建立

酒石酸泰乐菌素是我国目前常用的一种兽用大环内酯类抗生素[1],亦称泰农、泰乐霉素,可由放线菌属弗氏链霉菌经发酵提取而得到,有泰乐菌素碱、磷酸盐和酒石酸盐3种形态。本文建立的酒石酸泰乐菌素残留蛋白质的检验方法适用于酒石酸泰乐菌素残留蛋白质的限度检测[9]。分析验证表明该方法准确、可靠,重复性好,可用于控制酒石酸泰乐菌素中残留蛋白质的检测。     

浊度法测定酒石酸泰乐菌素可溶性粉效价研究

目的:建立浊度法测定酒石酸泰乐菌素可溶性粉效价的方法。方法:以金黄色葡萄球菌为试验菌,抗生素检定培养基Ⅲ号为试验用培养基,制备菌悬液。采用浊度法和管碟法对酒石酸泰乐菌素可溶性粉的效价测定进行比较,并对浊度法进行方法学验证。结果:用浊度法测定酒石酸泰乐菌素可溶性粉的效价,泰乐菌素的浓度范围在0.6-2.0 u/mL之间,其浓度对数与吸收度有良好的线性关系,相关系数r=0.999 0,平均回收率为100.3%,RSD为0.91%;用浊度法与管碟法测定结果无明显差异,方法学验证表明,浊度法测定酒石酸泰乐菌素可溶性粉效价的方法可行。结论:本方法具有可信限率低、灵敏度高、精密度高、快速简便等优点,可用于泰乐菌素及其制剂的效价测定。     

Comparative pharmacokinetics and bioavailability of tylosin tartrate and tylosin phosphate after a single oral and i.v. administration in chickens

The pharmacokinetics and oral bioavailability of tylosin tartrate and tylosin phosphate were carried out in broiler chickens according to a principle of single dose, random, parallel design. The two formulations of tylosin were given orally and intravenously at a dose level of 10 mg/kg b.w to chicken after an overnight fasting (n = 10 chickens/group). Serial blood samples were collected at different time points up to 24 h postdrug administration. A high performance liquid chromatography method was used for the determination of tylosin concentrations in chicken plasma. The tylosin plasma concentration's time plot of each chicken was analyzed by the 3P97 software. The pharmacokinetics of tylosin was best described by a one‐compartmental open model 1st absorption after oral administration. After intravenous administration the pharmacokinetics of tylosin was best described by a two‐compartmental open model, and there were no significant differences between tylosin tartrate and tylosin phosphate. After oral administration, there were significant differences in the C_max (0.18 ± 0.01, 0.44 ± 0.09) and AUC (0.82 ± 0.05, 1.57 ± 0.25)between tylosin phosphate and tylosin tartrate. The calculated oral bioavailability (F) of tylosin tartrate and tylosin phosphate were 25.78% and 13.73%, respectively. Above all, we can reasonably conclude that, the absorption of tylosin tartrate is better than tylosin phosphate after oral administration.     

Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and oral administration in pigs

The pharmacokinetics and dosage regimen of norfloxacin-glycine acetate (NFLXGA) was investigated in pigs after a single intravenous (i.v.) or oral (p.o.) administration at a dosage of 7.2 mg/kg body weight. After both i.v. and p.o. administration, plasma drug concentrations were best fitted to an open two-compartment model with a rapid distribution phase. After i.v. administration of NFLXGA, the distribution (t_1/2α) and elimination half-life (t_1/2β) were 0.36 ± 0.07 h and 7.42 ± 3.55 h, respectively. The volume of distribution of NFLXGA at steady state (Vd_ss) was 4.66 ± 1.39 l/kg. After p.o. administration of NFLXGA, the maximal absorption concentration (C_max) was 0.43 ± 0.06 µg/ml at 1.36 ± 0.39 h (T_max). The mean absorption (t_1/2ka) and elimination half-life (t_1/2β) of NFLXGA were 0.78 ± 0.27 h and 7.13 ± 1.41 h, respectively. The mean systemic bioavailability (F) after p.o. administration was 31.10 ± 15.16%. We suggest that the optimal dosage calculated from the pharmacokinetic parameters is 5.01 mg/kg per day i.v. or 16.12 mg/kg per day p.o.     

桔梗"引经"对罗红霉素肺药浓度的影响

罗红霉素与桔梗联合应用后,探讨桔梗对罗红霉素肺中药物浓度的影响.罗红霉素设三个剂量组,分别为每千克体重8 mg、10 mg、12 mg,桔梗均2 gkg(按生药量计算),对照组给予相同剂量的罗红霉素,采用微生物法检测桔梗与罗红霉素配伍后罗红霉素在肺组织中药物浓度.结果桔梗可使罗红霉素在肺组织中分布时间提前,提高了罗红霉素在肺组织中的药物浓度.结果表明桔梗的"引经作用"能提高肺组织中罗红霉素的药物浓度.     

桔梗对左氧氟沙星在健康鸡体内药动学影响的研究

为研究桔梗对左氧氟沙星（LVLX）在健康鸡体内的血药浓度及药动学参数的影响，72只健康鸡随机平均分成2组，Ⅰ组单剂量灌胃给予左氧氟沙星（10mg／kg）；Ⅱ组左氧氟沙星（10mg／kg）与桔梗煎液（2g／kg）联用。采用高效液相色谱法测定血药浓度，最低检测限0．001mg／L，并以3P97药动学程序进行分析，药时数据均符合一级吸收二室模型（权重=1）。与Ⅰ组相比，Ⅱ组的药动学参数有如下变化：T1/2α、T1/2ka增大，Cmax、ka降低，差异均不显著（P〉0．05）；T1/2β、Tmax、AUC、MRT0-36均极显著增加（P〈0．01）。结果表明：桔梗对左氧氟沙星在健康鸡体内的药物代谢有较大影响；减慢LVLX在体内的吸收速度，但增加了LVLX吸收的程度；加快了LVLX向组织的转运；减慢了LVLX在鸡体内的消除速度，延长了药物在体内的作用时间。     

Tolerance and pharmacokinetics of cephalexin in cats after oral administration

The tolerance of cephalexin in 10 cats was studied after oral administration of coated tablets (Cefaseptin; Chassot and Cie AG). Over a period of 21 days, the drug was administered twice daily at doses of 25, 30, 50 and 75 mg/kg body-weight. While the first three dose rates were well tolerated clinically, the highest dose was not. After seven days of treatment, signs of intolerance were salivation, vomiting and diarrhoea. Biochemical and haematological parameters (determined in blood, plasma and urine) were not altered. Plasma and skin concentrations of cephalexin were measured after oral treatment of cats with 25 and 50 mg cephalexin/kg body-weight. After treatment with 25 mg/kg body-weight, a mean elimination plasma half-life of 1–7 hours was calculated. The cephalexin concentration measured in the skin after two hours ranged from 8 to 22 per cent of the plasma level, so it is questionable if sufficiently high skin concentrations for efficacy are achieved with doses of 25 mg/kg body weight.     

Pharmacokinetics and tissue distribution of itraconazole after oral and intravenous administration to horses

OBJECTIVE: To determine the pharmacokinetics of itraconazole after IV or oral administration of a solution or capsules to horses and to examine disposition of itraconazole in the interstitial fluid (ISF), aqueous humor, and polymorphonuclear leukocytes after oral administration of the solution. ANIMALS: 6 healthy horses. PROCEDURE: Horses were administered itraconazole solution (5 mg/kg) by nasogastric tube, and samples of plasma, ISF, aqueous humor, and leukocytes were obtained. Horses were then administered itraconazole capsules (5 mg/kg), and plasma was obtained. Three horses were administered itraconazole (1.5 mg/kg, IV), and plasma samples were obtained. All samples were analyzed by use of high-performance liquid chromatography. Plasma protein binding was determined. Data were analyzed by compartmental and noncompartmental pharmacokinetic methods. RESULTS: Itraconazole reached higher mean +/- SD plasma concentrations after administration of the solution (0.41 +/- 0.13 microg/mL) versus the capsules (0.15 +/- 0.12 microg/mL). Bioavailability after administration of capsules relative to solution was 33.83 +/- 33.08%. Similar to other species, itraconazole has a high volume of distribution (6.3 +/- 0.94 L/kg) and a long half-life (11.3 +/- 2.84 hours). Itraconazole was not detected in the ISF, aqueous humor, or leukocytes. Plasma protein binding was 98.81 +/- 0.17%. CONCLUSIONS AND CLINICAL RELEVANCE: Itraconazole administered orally as a solution had higher, more consistent absorption than orally administered capsules and attained plasma concentrations that are inhibitory against fungi that infect horses. Administration of itraconazole solution (5 mg/kg, PO, q 24 h) is suggested for use in clinical trials to test the efficacy of itraconazole in horses.     

Plasma pharmacokinetics of quinocetone in ducks after oral and intravenous administration

Quinocetone (QCT), an antimicrobial growth promoter, is widely used in food‐producing animals. However, information about pharmacokinetics (PK) of QCT in ducks still remains unavailable up to now. In this study, QCT and its major metabolites (1‐desoxyquinocetone, di‐desoxyquinocetone and 3‐methyl‐quinoxaline‐2‐carboxylic) in ducks were studied using a simple and sensitive UHPLC‐MS/MS assay. Twenty ducks were divided into two groups. (n = 10/group). One group received QCT by oral administration at dose of 40 mg/kg while another group received QCT intravenously at 10 mg/kg. Plasma samples were collected at various time points from 0 to 96 hr. QCT and its major metabolites in duck plasma samples were extracted by 1 ml acetonitrile and detected by UHPLC‐MS/MS, with the gradient mobile phase that consisted of 0.1% formic acid in water (A) and acetonitrile (B). A noncompartment analysis was used to calculate the PK parameters. The results showed that following oral dosing, the peak plasma concentration (C_max) of QCT was 32.14 ng/ml and the area under the curve (AUCINF_obs) was 233.63 (h ng)/ ml. Following intravenous dosing, the C_max, AUCINF_obs and Vss_obs were 96.70 ng/ml, 152.34 (h ng)/ ml and 807.00 L/kg, respectively. These data indicated that the QCT was less absorbed in vivo following oral administration, with low bioavailability (38.43%). QCT and its major metabolites such as 1‐desoxyquinocetone and 3‐methyl‐quinoxaline‐2‐carboxylic were detected at individual time points in individual ducks, while the di‐desoxyquinocetone was not detected in all time points in all ducks. This study enriches basic scientific data about pharmacokinetics of QCT in ducks after oral and intravenous administration and will be beneficial for clinical application in ducks.     

Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and intramuscular administration to horses

The pharmacokinetic properties of norfloxacin-glycine acetate (NFLXGA) were determined in six horses following a single intravenous (i.v.) and intramuscular (i.m.) dose of 4 mgkg(-1) body weight. Following i.v. and i.m. administration, the plasma drug concentrations were best fitted by an open two-compartment model with a rapid distribution phase. After i.v. NFLXGA administration, the distribution (t(1/2alpha)) and elimination half-life (t(1/2beta)) were 0.42 (0.05) and 5.44 (1.36)h. The volume of distribution of NFLXGA at steady state (Vd(ss)) was 2.19 (0.53) Lkg(-1). After NFLXGA i.m. administration, the maximal absorption concentration (C(max)) was 0.44 (0.04) microgml(-1) at 0.86 (0.15)h (T(max)). The mean absorption (t(1/2ka)) and elimination half-life (t(1/2beta)) of NFLXGA were 0.27 (0.07) and 9.47 (2.24)h, respectively. The mean systemic bioavailability (F) following i.m. administration was 55 (12)%. The optimal dosage for each administration route was calculated from the pharmacokinetic data on the basis of the area under the inhibitory plasma concentration-time curve (AUIC) every 24h and was found to be 13.36 and 7.35 mgkg(-1) for i.m. and i.v. administration, respectively.