氟苯尼考在鲫和草鱼体内的药代/药效动力学联合参数及其临床给药方案的研究

为研究氟苯尼考在鲫和草鱼体内的药代学、药效动力学联合参数,并制定氟苯尼考对鲫、草鱼的精确用药方案,本实验结合氟苯尼考对致病性嗜水气单胞菌CAAh01的体外药效学研究和口灌不同剂量的氟苯尼考在鲫、草鱼体内药代动力学研究,确定了氟苯尼考防治该致病菌引起的鲫和草鱼细菌性败血症的给药方案。研究结果显示,氟苯尼考对CAAh01菌株的最小抑菌浓度(MIC)为0.5μg/mL,最小杀菌浓度(MBC)为1.0μg/mL,防细菌耐药突变浓度(MPC)为6.0μg/mL,防耐药突变选择窗(MSW)为0.5~6.0μg/mL。按10、20、30 mg/kg体质量剂量对鲫、草鱼口灌氟苯尼考后,在鲫体内,血药浓度大于MPC的维持时间分别为5、8、24 h;AUC24/MIC分别为177.06、265.90、426.50;Cmax/MIC分别为15.59、21.32、31.24。在草鱼体内,血药浓度大于MPC的维持时间分别为0、0、3 h;AUC24/MIC分别为38.60、75.08、121.94;Cmax/MIC分别为4.75、10.08、19.99。研究表明,综合血药浓度维持MPC以上的时间、AUC24/MIC或Cmax/MIC指标,氟苯尼考适用于鲫细菌性疾病的防治,其防突变用药方案为剂量30 mg/kg,每日1次给药,休药期不低于20 d。对于草鱼细菌性疾病的防治,氟苯尼考不宜连续使用。     

DYNAMIC CONTRAST‐ENHANCED MAGNETIC RESONANCE IMAGING OF CANINE BRAIN TUMORS

We evaluated dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) in canine brain tumors. Magnetic resonance data sets were collected on seven canine intracranial tumors with a 3 T magnet using a T1‐weighted fast spin echo fluid attenuated inversion recovery sequence after an IV bolus injection (0.2 mmol/kg) of Gd‐DTPA. The tumors were confirmed histopathologically as adenocarcinoma (n=1), ependymoma (n=1), meningioma (n=3), oligodendroglioma (n=1), and pituitary macroadenoma (n=1) The data were analyzed using a two‐compartment pharmacokinetic model for estimation of three enhancement parameters, E_R (rate of enhancement), K_el (rate of elimination), and K_ep (rate constant), and a model‐free phenomenologic parameter initial area under the Gd concentration curve (IAUGC) defined over the first 90 s postenhancement. Pearson's correlations were calculated between parameters of the two methods. The IAUGC has a relatively strong association with the rate of enhancement E_R, with r ranges from 0.4 to 0.9, but it was weakly associated with K_ep and K_el. To determine whether any two tumors differed significantly, the Kolmogorov–Smirnov test was used. The results showed that there were statistical differences (P<0.05) between distributions of the enhancement pattern of each tumor. These kinetic parameters may characterize the perfusion and vascular permeability of the tumors and the IAUGC may reflect blood flow, vascular permeability, and the fraction of interstitial space. The kinetic parameters and the IAUGC derived from DCE‐MRI present complementary information and they may be appropriate to noninvasively differentiate canine brain tumors although a larger prospective study is necessary.     

环丙沙星在大鼠体内的生理药动学模型的血流图设计

【目的】建立更能准确预测环丙沙星在大鼠体内药物浓度经时变化的生理药动学模型。【方法】通过搜集环丙沙星的理化性质、药动学特点及大鼠的生理生化参数,根据生理学和解剖学知识及质能守恒定律,对模型进行了必要的前提假设。【结果】成功设计了环丙沙星在大鼠的生理药动学模型的血流图。【结论】血流图的成功设计,为环丙沙星在大鼠的生理药动学模型的建立奠定了良好的基础。     

诺氟沙星在淡水青虾体内药物代谢动力学研究

在（26±1）℃的水温条件下,青虾一次性肌肉注射25mg／kg诺氟沙星后,用反相高效液相色谱法测定青虾血淋巴和肌肉组织中诺氟沙星含量。青虾血淋巴药一时曲线和肌肉药一时曲线均可以用二室开放模型来描述,诺氟沙星在青虾血淋巴液中的主要药动学参数为：分布相半衰期t1/α为1．66h,消除相半衰期t1/β为1．69h,达峰时间T（Peak）为1．82h,峰浓度C（max）为6．0081μg/mL,曲下面积AUC为30．75μg·mL^-1·h^-1,吸收相半衰期t1/2ka为1．66h。肌肉中的主要药动学参数为：分布相半衰期t1/ks为0．08h,消除相半衰期t1/2β为4．42h,达峰时间狄Peak）为0．03h,峰浓度C（max）为16．72μg/mL,曲下面积AUC为12．34μg·mL^-1·h^-1,吸收相半衰期t1/2a为0．08h。结果表明青虾肌注诺氟沙星后,能比较迅速的被吸收,并且在组织中维持较高的药物浓度。     

先锋霉素Ⅰ在马体内代谢动力学特征的研究

本文选用高效液相色谱(HPLC),测定先锋霉素I在4匹成年健康重挽马体内动力学过程。色谱柱采用反相ODS柱[25×4.6mm(ID))柱温35℃,流动相由甲醇:双重蒸馏水:36％醋酸:1.77％磷酸盐缓冲液(40:60:0.1:6)组成。流速为0.8 ml/min。紫外检测器波长为245nm。用高效液相色谱仪测定了不同时间血药浓度数据,符合开放式二室模型,用夏普PC—1500袖珍计算机处理数据。主要动力学参数如下:消除半衰期(t1/2β)为0.50±015(小时),分布半衰期(t1/2α)为0.05±0.01(小时),曲线下面积(AUC)为49.122±29.01(微克/毫升·小时),总表现分布容积(V_d)为0.3050±0.1488(升/公斤),总清除率(CIB)为0.3877±0.1418(毫升/公斤·小时),有效浓度维持时间[TCP(ther)]为2.78±0.49(小时)。按单剂量给药有关参数计算出多剂量给药参数如下:给药间隔时间(τ)为4小时,积累系数(R)为1.00,最高[(C∞)_(man))、平均(C)与最低((C∞)_(min)]稳态浓度分别为223.99(微克/毫升)、12.28(微克/毫升)与0.06(微克/毫升)。首次剂量(D_0~*)为15(毫克/公斤)。     

美洛昔康片剂在比格犬内的药代动力学及生物利用度研究

本研究以0.1 mg/kg体重的剂量研究美洛昔康片在比格犬中的药代动力学和生物利用度。HPLC分析血浆中的药物浓度,WinNonlin 6.4非房室模型计算药动学参数。比格犬内服美洛昔康片后测得0~48 h美洛昔康的T1/2、Cmax、Tmax和AUC0-t分别为14.55 ± 2.18 h、296.16 ± 74.15 ng·mL-1、6.0 ± 0.00 h和6356.79 ± 1089.78 ng·h·mL-1;比格犬静脉注射美洛昔康溶液后,测得0~48 h美洛昔康的T1/2和AUC0-t分别为11.54 ± 4.18 h和5510.68 ± 1075.29 ng·h·mL-1。内服美洛昔康片剂的绝对生物利用度为115.35%。美洛昔康片在比格犬体内消除速率较慢,消除半衰期较长,在体内滞留时间较长,绝对生物利用度高,药物在体内作用时间较长等药动学特征。     

Antibacterial efficacy and pharmacokinetic evaluation of sanguinarine in common carp (Cyprinus carpio) following a single intraperitoneal administration

Sanguinarine (SA), with antimicrobial and antiparasitic activities against fish pathogens, exhibits great potential commercial use in aquaculture. However, little information on pharmacokinetics of SA restricts further application in aquaculture. In this study, pharmacokinetics of SA in common carp (Cyprinus carpio) following a single intraperitoneal administration [10 mg kg^?1 BW (body weight)] was evaluated by high‐performance liquid chromatography (HPLC). The peak concentration (C_max) of SA in kidney was 11.8 μg g^?1, which was higher than in other tissues and plasma. The terminal half‐life in fish tissue and plasma was as follows: 42.3 h (kidney) > 37.2 h (liver) > 20.1 h (gill) > 18.8 h (muscle) > 10.9 h (spleen) > 10.0 h (plasma). Additionally, we determined the bacterial loads in tissues of common carp infected with Aeromonas hydrophila after i.p. administration of SA at 0, 5, 10 and 20 mg kg^?1 BW. The results showed that i.p. administration of SA at 10 mg kg^?1 BW significantly enhanced antibacterial efficacy against A. hydrophila, where the antibacterial ratio in the gill, kidney, spleen and liver on day 5 was 95.13%, 93.33%, 90.09% and 92.82%, respectively. Overall, these results suggested the potential of SA to treat A. hydrophila infection in common carp farming industry.     

Pharmacokinetics of minocycline in crucian carp (Carassius auratus) after intravenous and oral administration

The pharmacokinetic of minocycline was studied after a single intravenous as well as oral dose (5 mg/kg body weight) in crucian carp (Carassius auratus) reared in freshwater at 10°C. Plasma samples were randomly collected from six fish at each sampling time. Plasma concentrations were determined by high‐performance liquid chromatography and further subjected to noncompartmental analysis. Initial concentration of minocycline just after intravenous administration was calculated as 7.320 μg/ml, while the other parameters after intravenous injection were determined as flows: apparent elimination rate constant (λ_z) of 0.064 per hr, apparent elimination half‐life () of 10.82 hr, total body clearance (Cl) of 142.72 ml/hr/kg, volume of distribution (Vz) of 2,227.38 ml/kg and volume of distribution at steady‐state (Vss) of 1,937.08 ml/kg. While after oral administration, the λ_z, , mean absorption time (MAT), absorption half‐life (t_1/2ka) and bioavailability were determined as 0.059 per hr, 11.74, 5.55, 3.84 hr, and 81.98%, respectively, and the peak concentration was observed as 1.474 ± 0.362 μg/ml at 8 hr. It was shown that minocycline was slowly but relatively completely absorbed, extensively distributed, and slowly eliminated in crucian carp. Based on the ratios of AUC_0–24 hr/MIC90, a minocycline dosage of 5 mg/kg body weight administered intravenously or orally would be only effective to successfully treat crucian carp infected by bacterium with MIC values ≤0.25 μg/ml.     

盐酸氯苯胍在兔体内的药动学及生物利用度研究

【目的】研究抗球虫药盐酸氯苯胍在家兔体内的药物代谢动力学特征及内服给药的生物利用度。【方法】16只健康新西兰大白兔,公母各半,分为2组,一组以2.00 mg·kg~(-1)单次静脉注射给药,另一组以100.00 mg·kg~(-1)单次内服给药,通过耳部静脉采血,并用HPLC-UV法检测血浆中的盐酸氯苯胍浓度。使用WinnonlinTM药动学软件非房室模型计算相关药动学参数,采用SPSS 16.0软件得到药时曲线图。【结果】兔静脉注射盐酸氯苯胍(2.00mg·kg~(-1))后,药-时曲线下面积为1.72μg·h·m L~(-1),血浆清除率为1.17 L·h~(-1)·kg~(-1),表观分布容积为2.87L·kg~(-1),消除半衰期为1.72 h;内服盐酸氯苯胍(100.00 mg·kg~(-1))后,药-时曲线下面积为6.33μg·h·m L~(-1),消除半衰期为8.94 h。盐酸氯苯胍2种给药方式的药动学参数均存在显著差异(P0.05),内服给药的生物利用度较低,仅为7.36%。【结论】盐酸氯苯胍静脉注射给药的表观分布容积较大,药物在兔组织中分布广泛,并且消除迅速;内服盐酸氯苯胍后,药物经肠道吸收的量较少,体内药物残留较低。