Interactions between erythromycin,flunixin meglumine,levamisole and plant secondary metabolites towards bovine gastrointestinal motility—in vitro study

Continued ingestion of plant secondary metabolites by ruminants can provoke pharmacological interactions with pharmaceutical agents used in animals. As some drugs and phytocompounds affect smooth muscle activity, the aim of this study was to verify the possible interaction between selected pharmaceutical agents and plant secondary metabolites towards bovine gastrointestinal motility. The interactions between phytocompounds—apigenin, quercetin, hederagenin, medicagenic acid—and medicines—erythromycin, flunixin meglumine and levamisole—were evaluated on bovine isolated abomasal and duodenal specimens obtained from routinely slaughtered cows. The obtained results confirmed the contractile effect of all three drugs used solely. Hederagenin and medicagenic acid (0.001 μM) enhanced the contractile effect of levamisole. Hederagenin additionally increased the impact of erythromycin. Both saponins (100 μM) showed synergistic effects with all tested pharmaceuticals. Apigenin and quercetin (0.001 μM) intensified the contractile response induced by erythromycin and levamisole. Moreover, both flavonoids (100 μM) showed an antagonistic interaction with all tested drugs which in that situation were devoid of the prokinetic effect. To conclude, plant metabolic metabolites such as saponins and flavonoids are potent modifiers of the effect of drugs towards gut motility. The synergy observed between phytocompounds and selected medicines can be beneficial in the treatment of cows with hypomotility disorders.     

Behavioral and performance response associated with administration of intravenous flunixin meglumine or oral meloxicam immediately prior to surgical castration in bull calves

The objective of this study was to determine the effects of flunixin meglumine or meloxicam on behavioral response and performance characteristics associated with surgical castration in crossbred bulls. Intact male Bos taurus calves (n = 252; averaging 176 kg) were randomly allocated into one of three treatment groups within pen: control (CON), flunixin meglumine (FLU; 2.2 mg/kg intravenous injection), or meloxicam (MEL; 2.0 mg/kg per os). The individual animal was the experimental unit. Calves were individually weighed on days 0 and 14 of the trial to evaluate performance outcomes. On study day 0, treatments were administered, according to their random allocation, immediately prior to surgical castration using the Henderson tool method. Visual analog scale (VAS) assessment and categorical attitude score (CAS) were collected on days −1, 0 (6 h post-castration), 1, 2, 3, and 4 in the study. The VAS was assigned using a 100 mm horizontal line with “normal” labeled at one end of the line and “moribund” at the other end of the horizontal line. The masked observer assigned a mark on the horizontal line based upon the observed severity of pain exhibited by that individual animal. The CAS was assigned by the same observer using five different categories with a score of 0 being “normal”. Average daily gain tended (P = 0.09) to be associated with the treatment group, and MEL had a greater (P = 0.04) average daily gain through day 14 compared with CON. A significant (P < 0.01) treatment by day interaction was indicated for VAS score, and MEL had lower VAS scores on days 0, 1, 2, and 3 post-castration compared with CON; FLU had lower VAS scores on days 0 and 1 compared with CON. A significant treatment by day interaction was not present (P = 0.25) for CAS. The FLU had lesser percent CAS ≥1 (17.5%; P = 0.05) compared with CON (29.4%); MEL has lesser percent CAS ≥1 observations (14.9%; P = 0.01) compared with CON. The median VAS increased as CAS was more severe. Results indicated MEL and FLU calves temporally improved behavioral responses following surgical castration with positive numerical trends for a 14 d average daily gain (ADG). The VAS system appeared to be an effective method of subjective evaluation of pain in beef calves in this study. Route of administration, duration of therapy, and low relative cost make oral meloxicam a reasonable analgesic treatment in calves when administered at the time of surgical castration.     

干扰素脂质体凝胶剂体外透皮扩散的效果观察

目的比较干扰素脂质体凝胶与干扰素凝胶在离体皮肤渗透的效果。方法干扰素脂质体凝胶剂与干扰素凝胶剂分别涂抹于对称的离体大鼠背部皮肤(有效扩散面积为8.04cm2),并置于改良Franz扩散池上,透皮扩散24h后检测皮肤层、凝胶层中的药物含量和接受液中的累计透过量。结果干扰素脂质体凝胶组皮肤层中干扰素的含量高于干扰素凝胶组,差异有统计学意义(P<0.01)。脂质体凝胶中的干扰素在皮肤层的含量约占总量的39.5%,凝胶中的干扰素在皮肤层的含量约占总量的18.4%。结论脂质体有促进干扰素渗入皮肤的作用,干扰素脂质体凝胶剂有可能成为干扰素的一种外用剂型。     

不同促透剂运用于隔药饼灸对高脂血症合并动脉粥样硬化兔主动脉形态及血清IL-6、IL-10的影响

目的 探讨氮酮和冰片作为促透剂运用于隔药饼灸对高脂血症合并动脉粥样硬化兔主动脉病理形态及血清炎症因子的影响。方法 选取40只新西兰纯种兔随机分成5组,每组8只,即正常组、模型组、无促透剂组、氮酮组和冰片组。高脂血症合并动脉粥样硬化兔模型造模成功后除正常组和模型组外,其余各组采用隔药饼灸干预,每日1次,连续4周。采用ELISA检测血清白细胞介素6（Interleukin 6,IL-6）、白细胞介素10（Interleukin 10,IL-10）含量;采用HE染色,光学显微镜下观察主动脉组织形态。结果 与正常组比,模型组IL-6水平显著升高、IL-10水平显著降低（P<0.01）;与模型组比,无促透剂组、氮酮组及冰片组IL-6水平显著降低（P<0.01）、IL-10水平升高（P<0.05）;与无促透剂比,氮酮组和冰片组IL-6水平显著降低（P<0.01）、IL-10差异无统计学意义（P>0.05）;与氮酮组比,冰片组IL-6水平显著降低（P<0.01）、IL-10差异无统计学意义（P>0.05）。主动脉组织镜检结果示：正常组无异常;模型组可见组织整体凌乱,管腔壁可见明显增厚,内皮坏死,有明显的脂质斑块及泡沫细胞;无促透剂组有内膜增厚,可见少量泡沫细胞,细胞排列较模型组稍好,脂质沉积明显较模型组减少,斑块不明显;氮酮组和冰片组无显著异常。结论 隔药饼灸对高脂血症合并动脉粥样硬化兔具有抑制炎症反应和抗动脉粥样硬化作用,在药饼中加入促透剂后施灸疗效更优,可能与药饼中药物透皮吸收增强有关,值得进一步临床应用和研究。     

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.     

复方特比萘芬纳米乳的皮肤安全性及经皮渗透性试验

考察复方特比萘芬纳米乳的透皮特性及皮肤毒性,为其临床应用提供试验依据。应用皮肤刺激性试验、皮肤急性毒性试验及皮肤过敏性试验考察复方特比萘芬纳米乳的皮肤安全性;采用改良的Franz立式扩散池,对复方特比萘芬纳米乳进行体外经皮透过性评价。结果显示,复方特比萘芬纳米乳对家兔无皮肤刺激性和皮肤急性毒性,对豚鼠皮肤无致敏性。复方特比萘芬纳米乳中特比萘芬与其混悬液的透皮速率(J)分别为0.840 3μg/cm.h和0.266 8μg/cm.h。表明复方特比萘芬纳米乳是一种安全性较好的外用制剂,且纳米乳增强了特比萘芬的经皮透过性。     

透皮给药后吡喹酮在小鼠体内组织分布及药代动力学

目的研究透皮给药后吡喹酮在小鼠体内的组织分布及药代动力学。方法用200mg/mL吡喹酮透皮剂涂擦小鼠腹部后,采用高效液相色谱法检测各时间点小鼠器官(肝、心脏、脾和肾)的吡喹酮浓度,分析其在各器官药代谢动力学特点。结果透皮给药后吡喹酮在小鼠肝脏分布浓度最高,脾和肾次之,心脏的浓度最低。吡喹酮在小鼠肝脏、脾和肾脏c-t曲线,各出现两个峰值,第一个峰值4min,Cmax分别为31.78μg/mL和7.87μg/mL,第二个峰值15min,Cmax分别为27μg/mL,11.1μg/mL。小鼠心脏的c-t曲线,有一个峰值3min,Cmax3.91μg/mL。结论吡喹酮透皮给药后,在小鼠肝脏分布浓度高,达到了临床治疗的要求。     

微乳透皮给药机制及影响吸收的因素

微乳能够提高药物溶解度,作用于皮肤角质层、皮肤附属器进而促进药物的透皮吸收,影响药物透皮吸收的因素主要是微乳中的各个组分以及所承载的药物特性。微乳用于经皮给药制剂将会有更广阔的应用前景和发展空间。文章综述了微乳透皮给药的吸收机制以及影响微乳透皮吸收的因素。