Development of a multiroute physiologically based pharmacokinetic model for orbifloxacin in rabbits

To predict the orbifloxacin concentrations in rabbits after multiple routes of administration, a flow‐limited multiroute physiologically based pharmacokinetic (PBPK) model was developed. Three routes of administration (IV, IM, and PO) were incorporated into this model. Physiological parameters including tissue weights and blood flows through different tissues were obtained from the literature. The tissue/plasma partition coefficients (P_Xs) for noneliminating tissues were calculated according to the area method, while the P_Xs for kidney and the rest of the body compartment, together with other parameters for absorption and elimination, were optimized based on the published concentrations. The comparisons between predicted and observed orbifloxacin concentrations proved its validity, and the present model predicted available concentration data well, including those in liver, kidney, muscle, lung, heart, and plasma after oral, intravenous, or intramuscular administration. A local sensitivity analysis was also performed, which showed that the parameters for oral absorption were most influential on the orbifloxacin concentrations. This model was used to predict plasma and tissue concentrations after multiple oral or intramuscular administration. This study demonstrated the feasibility of predicting drug residues in minor species after multiple routes of administration in the extra‐label manner using the PBPK modeling.     

力克斯兔被毛细度,粗毛度和皮板厚度研究

于冬（１２月下旬－１月上旬）夏（６月下旬－７月上旬）两季分别随机选取１－６月龄的美系獭兔各５只，屠杀后取皮，自然伸展后晾皮，待其干燥后分别取样测定不同部位的被毛粗毛率、细度和皮板厚度。结果表明，美系獭兔的被毛粗毛率平均为５．４９％；被毛细度平均为１６．３３μｍ；４、５、６月龄獭兔皮板厚度分别为０．５０ｍｍ、０．５７ｍｍ和０．６５ｍｍ。三项指标在不同部位、季节和月龄等方面均有一定的变化，而背的中部具     

酵母铬对獭兔生长性能和血清生化指标的影响

选择30±2日龄平均体重0．78±0．04kg的健康獭兔96只，按体重和性别随机分为4组，每组24只，分别饲喂基础日粮、基础日粮＋200μg／kg酵母铬、基础日粮＋400μg/kg酵母铬、基础日粮＋800μg/kg酵母铬4种日粮，试验期60d。结果表明，基础日粮添加400μg／kg酵母铬，能显著提高獭兔断奶后15d内日增重（P〈0．01）；日粮补铬能降低獭兔血清葡萄糖、总甘油三酯、总胆固醇、低脂蛋白胆固醇水平，升高高脂蛋白胆固醇水平，但对蛋白质水平无显著影响。     

新西兰白兔MSTN基因克隆、生物信息学分析及表达谱构建

肌肉生长抑制素（MSTN）是骨骼肌发育的主要调控因子，为获得新西兰白兔MSTN基因序列及其表达规律，试验通过RT-PCR技术从新西兰白兔腿肌组织中扩增并克隆得到MSTN基因序列，利用在线网站对其进行生物信息学分析，并采用实时荧光定量PCR技术检测MSTN基因在新西兰白兔同一时期不同组织及不同时期腿肌组织中的表达量。结果显示，新西兰白兔MSTN基因CDS区序列长1 128 bp，编码375个氨基酸，其核苷酸序列与GenBank上公布的人、猪、马、小鼠、犬、牛和鸡的核苷酸序列相似性分别为95.9%、94.9%、94.9%、91.7%、91.5%、91.3%及84.2%。新西兰白兔MSTN蛋白属于酸性、亲水性分泌蛋白，且具有不稳定性，不含跨膜结构，含有1个信号肽，主要分布在内质网和线粒体中。MSTN蛋白二级结构和三级结构预测结果一致，以无规则卷曲为主，其次是α-螺旋、延伸链，为混合型蛋白。蛋白质互作关系预测发现，MSTN蛋白与PAX7、MYOG、IGF1、FST、Smad3及Smad2等与肌肉生长发育有关的蛋白之间存在相互作用。不同组织表达分析结果表明，新西兰白兔MSTN基因在心脏、肝脏、脾脏、肺脏、肾脏、腿肌、子宫和胃中均有表达，在腿肌中表达量最高，极显著高于其他组织（P<0.01），其次是肾脏，在肝脏中的表达量最低。不同时期腿肌组织中的表达量分析结果显示，新西兰白兔MSTN基因在180日龄腿肌组织中的表达量显著高于90和240日龄（P<0.05）。研究结果为深入探讨MSTN基因对家兔肌肉生长发育的调控机制奠定了基础。     

Sedative and cardiorespiratory effects of intranasal atomized alfaxalone in Japanese White rabbits

ObjectiveTo investigate the sedative and cardiorespiratory effects of intranasal atomization (INA) of alfaxalone using a mucosal atomization device in Japanese White rabbits.Study designRandomized, prospective, crossover study.AnimalsA total of eight healthy female rabbits, weighing 3.6–4.3 kg and aged 12–24 months.MethodsEach rabbit was randomly assigned to four INA treatments administered 7 days apart: Control treatment, 0.15 mL 0.9% saline in both nostrils; treatment INA0.3, 0.15 mL 4% alfaxalone in both nostrils; treatment INA0.6, 0.3 mL 4% alfaxalone in both nostrils; treatment INA0.9, 0.3 mL 4% alfaxalone in left, then right, then left nostril. Sedation was scored 0–13 using a composite measure scoring system for rabbits. Simultaneously, pulse rate (PR), respiratory rate (f_R), noninvasive mean arterial pressure (MAP), peripheral hemoglobin oxygen saturation (SpO₂) and arterial blood gases were measured until 120 minutes. The rabbits breathed room air during the experiment and were administered flow-by oxygen when hypoxemia (SpO₂ <90% or PaO₂ <60 mmHg; 8.0 kPa) developed. Data were analyzed using the Fisher's exact test and the Friedman test (p < 0.05).ResultsNo rabbit was sedated in treatments Control and INA0.3. All rabbits in treatment INA0.9 developed loss of righting reflex for 15 (10–20) minutes [median (25th–75th percentile)]. Sedation score significantly increased from 5 to 30 minutes in treatments INA0.6 and INA0.9 with maximum scores of 2 (1–4) and 9 (9–9), respectively. f_R decreased in an alfaxalone dose-dependent manner and one rabbit developed hypoxemia in treatment INA0.9. No significant changes were observed in PR and MAP.Conclusions and clinical relevanceINA alfaxalone resulted in dose-dependent sedation and respiratory depression in Japanese White rabbits to values considered not clinically relevant. Further investigation of INA alfaxalone in combination with other drugs is warranted.     

Pharmacokinetics of Flunixin after Intravenous Administration in Healthy and Endotoxaemic Rabbits

The pharmacokinetics of flunixin were determined after intravenous bolus injection at a single dose (2.2 mg/kg) in healthy rabbits and diseased rabbits with Escherichia coli lipopolysaccharide-induced septic shock. Six adult New Zealand White rabbits were used. Concentrations of drug in plasma were determined by HPLC. Pharmacokinetics were best described by a two-compartment open model. In healthy rabbits, there was a high plasma clearance (0.62 L/(h kg)), and a relatively short elimination half-life (1.19 h). In endotoxaemic rabbits, total plasma clearance (0.43 L/(h kg)) was significantly lower (p<0.05), and elimination half-life (1.90 h) and AUC₀-∞ (5.29 (μg h)/ml) were significantly higher (p<0.05) than in healthy animals. The changes of pharmacokinetics of flunixin in rabbits with septic shock could be of clinical significance, and may require monitoring of plasma flunixin levels in endotoxaemic status.     

皖江长毛兔生长兔饲料配方的筛选

选择42日龄断奶皖江长毛兔42只,随机分成3组,每组公母各半。分别饲喂三种日粮。结果表明：试验1组产毛量比对照组和试验2组分别提高7．4％和1．8％,粗毛率比对照组提高5．66％,但略低于试验2组;试验1组、试验2组粗毛长度比对照组分别长16．7％和20.3％．细毛长度比对照组分别长6．5％和10．0％;粗毛、细毛间强度和伸度均无显著差异,但试验组比对照组有所提高：平均耗料量,试验1组比对照组、试验2组少0．9％和6．2％,试验2组比对照组多耗料5．6％,但各组间差异不显著：试验1组、试验2组增重比对照组分别提高11．2％和12．5％;试验1组的经济效益高于其他两组。试验1组的饲料配方为最适配方。     

美系獭兔和苏Ⅰ系粗毛型长毛兔的遗传多样性分析

采用15个微卫星标记,对关系獭免和苏Ⅰ系粗毛型长毛兔进行了遗传多样性分析。结果显示：在美系獭兔和苏Ⅰ系粗毛型长毛兔群体中,15个微卫星座位均表现出较好的多态性。关系獭兔的平均等位基因数和有效等位基因数分别为4．6000±1．0556和3．5520±0．9703个．群体期望杂合度和多态信息含量平均值分别为0．7067±0．1030和0．6501±0．1050,群体内近交系数平均值为-0．2580＋0．0033：苏Ⅰ系粗毛型长毛免的平均等位基因数和有效等位基因数分别为5．1333±1．2459和3．7506±0．8081个,群体期望杂合度和多态信息含量平均值分别为0．7270±0．0709和0．6750±0．0824．群体内近交系数平均值为-0．2300±0．003。表明两个家兔群体的微卫星座位有丰富的遗传多样性。     

热应激对獭兔血液生化指标的影响

热应激使獭兔血液生化指标发生改变,从而使獭兔的生产性能受到严重影响。试验结果表明,在热应激状态下,随着温度升高,各试验组獭兔血清葡萄糖含量升高,血清总胆固醇含量降低,血清甘油三酯含量则极显著升高;热应激使獭兔血清钙离子和血清无机磷含量降低,而血清氯化物含量和血清钾离子含量则随温度升高而升高。     

獭兔早期生长发育规律及生长曲线的拟合

采用Logistic生长曲线原理对獭兔生长期生长曲线进行拟合,建立獭兔生长曲线方程,探索獭兔的生长规律。结果表明：①根据Logistic生长曲线方程原理,确定了獭免生长曲线方程参数a=24．1504,b=1．2402,并对方程进行了拟合,建立了獭兔生长曲线方程y=2949／（1＋24．1504e-1．2402x）（P〈0．05）;②Logistic方程能很好地拟合獭兔的生长过程,拟合度均在0．95以上,生长的拐点时间为2．97月龄,拐点体重为2298．28g,极限体重参数2949g。