Sustained availability of trimethoprim in drinking water to achieve higher plasma sulphonamide-trimethoprim antibacterial activity in broilers

(1) In order to make trimethoprim (TMP) available to broilers throughout the day, a sustained release formulation (SRF) of the drug in the form of granules was added to the water tank that supplies drinking water. (2) Broilers were initially dosed with sulphachloropiridazine-TMP (SCP-TMP 5:1) and then further medicated throughout the day, achieving in the end a dose of 30 mg/kg each of SCP and TMP (group A). Group B received a preparation with the same dose of SCP and TMP (1:1) as group A, but administered as a single dose without the SRF of TMP. Group C received the customary SCP-TMP 5:1 preparation (30 and 6 mg/kg, respectively). Water tanks were completely consumed in 3 to 4 h. (3) Broilers were bled at different times and concentration of antibacterial activity in serum determined by correlating the composite antibacterial activity of SCP and TMP with actual concentrations of these drugs by means of a microbiological agar diffusion assay. (4) Time vs serum concentrations of activity were higher in group B; the increments in the maximum serum concentration for group B over groups A and C being 39 and 67%, respectively. (5) However, the sustained concentration of activity over time, measured as the area under the cu)rve, was highest in group A. Group B had higher values for area under the curve than group C. (6) An additional dose of TMP to achieve 30 mg/kg of both SCP and TMP improves the serum concentration of this combination over the customary 5:1 proportion. The best values for sustaining antibacterial activity were obtained using a 1:1 ratio as in group A. The use of a SRF as in group A may translate into better clinical results.     

Circadian serum concentrations of tylosin in broilers after feed or water medication

1. Because tylosin is a time-dependent antibacterial agent, and because feeding and drinking of broilers decreases in late afternoon and ceases in the dark, it was hypothesised that serum concentrations of this drug are greatly reduced during the dark period. 2. The trial was carried out in a commercial poultry house, under standard broiler husbandry conditions, with food and water withdrawn from 22:00 until 07:00 h next morning and exposed to a natural light cycle of 13L:11D. 3. Broilers were given tylosin tartrate, in either feed or water, for 5 d as follows: 100, 200 and 300 ppm in feed, equivalent to 12.6, 25.2 and 37.8 mg/kg/d, respectively; and 200 and 400 mg/l in drinking water, equivalent to 51 to 102 mg/kg/d, respectively. 4. At 07:00 h on d 4, and for the next 40 h, hourly serum samples were obtained and analysed for tylosin by means of a microbiological assay. 5. Day vs night concentrations of tylosin expressed as area under the curve (AUC) in all groups revealed greater values during the day. The highest AUC and AUC(24)/minimal inhibitory concentration (MIC) ratio were obtained in the group medicated with 400 mg/l and the corresponding lowest values were found in the group medicated with 100 ppm in feed. 6. In conclusion, tylosin did not reach therapeutic serum concentrations during the dark period, at all dose rates tested when administered in feed or water. A sustained release form of this drug is needed to solve this inadequacy of tylosin medication in broilers.     

Strategic administration of enrofloxacin in poultry to achieve higher maximal serum concentrations

To achieve a higher maximal serum concentration (Cs(max)) of enrofloxacin after oral administration of 10mg/kg/day of three commercial preparations of enrofloxacin to chickens, two concentrations of the drug were tested (0.1 and 0.2%), under controlled laboratory conditions. A single oral bolus dose was delivered directly into the proventriculus of each of 240 chickens, which were equally divided into six groups: three received the customary concentration (0.1%), and three received the higher concentration. A quantitative/qualitative microbiological analytical method to determine serum concentrations of enrofloxacin and a software program to obtain pharmacokinetic variables, revealed that time vs. concentration relationships best fitted double peak shape curves, Cs(max1) and Cs(max2). Statistically significant (P>0.01) increments were obtained when 0.2% enrofloxacin oral solutions from the three different commercial preparations were administered. The increments ranged from 175% to 338% for Cs(max1) and 69% to 342% for Cs(max2). Optimal bactericidal concentrations of enrofloxacin are usually twice the value of their minimal inhibitory concentration. Although clinical trials are now required, it would appear that increments in the serum concentration of enrofloxacin may reduce to the rate at which bacterial resistance occurs and so increase clinical efficacy without affecting the cost per treatment.     

Effect of enrofloxacin therapy on shipping fever pneumonia in feedlot cattle

The effect of enrofloxacin therapy was investigated in 110 male double-muscled cattle weighing 275 +/- 3 kg, during a spontaneous outbreak of shipping fever occurring 11 +/- 2 days after they arrived in the feedlot. Forty-six diseased animals were divided randomly into three groups A, B and C, containing 17, 19 and 10 animals, respectively; the animals in group A were injected intramuscularly once daily for three consecutive days with 2.5 mg/kg of enrofloxacin, those in group B with 5 mg/kg of enrofloxacin and those in group C with 10 mg/kg of oxytetracycline. Clinical, serological, production and respiratory functional observations were recorded. The animals were clinically cured after the three day treatment except for three in group A and two in group C. These five animals made a clinical recovery after a three day booster treatment with a dose of 5 mg/kg enrofloxacin. The changes in respiratory gas exchange values induced by shipping fever were completely reversed 15 days later, suggesting that there had been no irreversible lung damage. The daily weight gains and the arterial blood gas values of the three groups of treated cattle were not significantly different. The high efficacy of the low dosage of enrofloxacin in this clinical syndrome may be explained by its antibacterial activity against Pasteurella species and Mycoplasma species. This field trial supports the in vitro studies which suggested than enrofloxacin is an appropriate therapy in cases of shipping fever.     

Non-bioequivalence of various trademarks of enrofloxacin and Baytril in cows

Including Baytril, in various parts of the world many commercial preparations of enrofloxacin for parenteral administration are being employed for the treatment of bacterial diseases in cows. To optimize clinical responses and to minimize development of bacterial resistance to this agent, the copied pharmaceutical preparations must comply with some key pharmacokinetic features when bioequivalence studies are performed. To assess whether or not there was bioequivalence among nine commercial preparations of enrofloxacin and the original one, a controlled pharmacokinetic study was carried out. These was done utilizing the microbiological agar-diffusion test as quantitative/qualitative analytical method. A non-compartmental model defined kinetic variables. Results for Baytril revealed that maximal serum concentration (Csmax) was only matched by one preparation while area under the curve (AUC) of the serum concentration/activity of enrofloxacin and metabolites in time was not matched by any preparation. Time to Csmax (Tmax), elimination half-life, and shape of the time-serum concentrations of enrofloxacin profiles obtained for the nine generic preparations differ significantly somehow from the corresponding data obtained for the reference enrofloxacin. The need for studies to demonstrate bioequivalence becomes mandatory if similar preparations of enrofloxacin become commercially available. Enrofloxacin should be used selectively and cautiously to limit development of bacterial resistance. Non-bioequivalence of relevant pharmacokinetic values, such as Csmax and bioavailability (AUC) would facilitate development of bacterial resistance and limit the useful life span of this antibacterial agent.     

Enrofloxacin pharmacokinetics in the European cuttlefish, Sepia officinalis, after a single i.v. injection and bath administration

Enrofloxacin pharmacokinetics were studied in European cuttlefish, Sepia officinalis, after a single 5 mg/kg i.v. injection or a 2.5 mg/L 5 h bath. A pilot study with two animals was also performed following a 10 mg/kg p.o. administration. The concentration of enrofloxacin in hemolymph was assayed using high-performance liquid chromatography (HPLC) and pharmacokinetic parameters were derived from compartmental methods. In the i.v. study, the terminal half-life (t(1/2)), apparent volume of distribution, and systemic clearance were respectively 1.81 h, 385 mL/kg, and 4.71 mL/min/kg. Following bath administration the t(1/2), peak hemolymph concentration (C(max)), and area under the curve to infinity (AUC(0-infinity)) were 1.01 h, 0.5 +/- 0.12 mug/mL, and 0.98 microg.h/mL, respectively. After oral administration, the t(1/2), C(max), and AUC(0-infinity) were 1.01 h, 10.95 microg/mL, 26.71 mug.h/mL, respectively. The active metabolite of enrofloxacin, ciprofloxacin, was not detected in any samples tested. The hemolymph concentration was still above minimum inhibitory concentration (MIC) values for shrimp and fish bacterial isolates at 6 h after i.v. administration, therefore, a dose of 5 mg/kg i.v. every 8-12 h is suggested for additional studies of efficacy. The C(max) value for the water bath was lower than for the i.v. study, but a bath of 2.5 mg/L for 5 h once to twice daily is suggested for additional studies to test efficacy against highly susceptible organisms. Although only two animals were used for the oral study, a dose of 10 mg/kg produced hemolymph concentrations of enrofloxacin that were in a range consistent with therapeutic efficacy in other species.     

Pharmacokinetic behaviour of enrofloxacin in greater rheas following a single-dose intramuscular administration

The pharmacokinetic behaviour of enrofloxacin in greater rheas was investigated after intramuscular (IM) administration of 15 mg/kg. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by high performance liquid chromatography. Enrofloxacin peak plasma concentration (C(max)=3.30+/-0.90 microg/mL) was reached at 24.17+/-9.17 min. The terminal half-life (t(1/2lambda)) and area under the curve (AUC) were 2.85+/-0.54 h and 4.18+/-0.69 microg h/mL, respectively. The AUC and C(max) for ciprofloxacin were 0.25+/-0.06 microg/mL and 0.66+/-0.16 microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, an IM dose of 15 mg/kg of enrofloxacin would appear to be adequate for treating infections caused by highly susceptible bacteria (MIC(90)<0.03 microg/mL) in greater rheas.     

有机硒和枣粉对肉仔鸡生长性能及养分利用的影响

为探究有机硒和枣粉对肉仔鸡生长性能及养分利用的影响,试验采用2×5两因子（A、B）随机试验设计,A因子为枣粉添加水平,分别为0、8%,B因子为硒添加水平,分别为 0、0.3、0.6、0.9、1.2 mg/kg。选择体重接近、健康的1日龄科宝505白羽肉仔鸡720只,随机分为 10组,每组 6 个重复,每个重复 12 只鸡（公母各半）。试验期为 42 d,分前期（0 ～ 21 d）和后期（22 ～ 42 d）两个饲养阶段。结果表明：有机硒和枣粉两因子间对肉仔鸡生长性能和养分利用均无显著的交互作用（P > 0.05）。试验前期,A2组平均日增重显著高于A1组（P < 0.05）,且A2组料重比显著低于其他各组（P < 0.05）|添加枣粉可显著提高肉仔鸡平均日采食量和料重比（P < 0.05）。试验后期,A5组平均日增重显著高于除A1组外的其他各组（P < 0.05）,而料重比显著低于除A3组外的其他各组（P < 0.05）,A4组平均日采食量显著高于A1、A2和A3组（P < 0.05）。A5组总能和总磷利用率均有下降的趋势（P =0.090|P =0.078）。添加枣粉后,肉仔鸡对氮和钙的利用率均有改善（P < 0.05）,但总能的利用率显著下降（P < 0.05）。综上,饲粮添加0.3 mg/kg硒可以提高肉仔鸡前期平均日增重,添加枣粉可改善肉仔鸡前期采食量,并提高氮和钙的利用率。 [关键词] 肉鸡|枣粉|有机硒|生长性能|养分利用     

Comparative serum pharmacokinetics of the fluoroquinolones enrofloxacin, difloxacin, marbofloxacin, and orbifloxacin in dogs after single oral administration

The pharmacokinetics after oral application of the fluoroquinolones (FQs), enrofloxacin, difloxacin, marbofloxacin and orbifloxacin were compared in independent crossover studies in Beagle dogs. Commercially available tablet formulations were given at common dosage recommended by the manufacturers which were 2.0 mg/kg body weight (bw) for marbofloxacin, 2.5 mg/kg bw for orbifloxacin and 5.0 mg/kg bw for enrofloxacin and difloxacin. Analysis was performed by an agar diffusion assay. Pharmacokinetic parameters were calculated by noncompartmental methods. All FQs were rapidly absorbed and achieved average peak serum concentrations of 1.41, 1.11, 1.47 and 1.37 mug/mL for enrofloxacin, difloxacin, marbofloxacin and orbifloxacin, respectively. Enrofloxacin was eliminated at a terminal half-life (t(1/2)) of 4.1 h, difloxacin at 6.9 h, orbifloxacin at 7.1 h and marbofloxacin at 9.1 h. While the area under the serum concentration-time curve of the 24-h dosing interval (AUC0--24) for marbofloxacin and orbifloxacin were similar (approximately 13 microg x h/mL), enrofloxacin attained an AUC(0-24) of 8.7 and difloxacin of 9.3 microg x h/mL. Because of its favourable pharmacokinetics combined with excellent in vitro activity, enrofloxacin exhibited superior pharmacodynamic predictors of in vivo antimicrobial activity as C(max)/MIC (maximum serum concentration/minimum inhibitory concentration) and AUC(0-24)/MIC (area under the 24-h serum concentration--time curve/minimum inhibitory concentration) compared with other FQs.     

不同水平丁酸钠对肉仔鸡养分利用率的影响

为了研究不同添加水平包膜和不包膜(粉剂)丁酸钠对肉仔鸡养分利用率的影响,本研究选用42日龄爱拔益加(AA)肉仔鸡72只,随机分为9个处理,每个处理4个重复,每个重复2只鸡。分别饲喂对应日粮:处理A为基础日粮;处理B为基础日粮+抗生素(杆菌肽锌40mg/kg+硫酸粘杆菌素8mg/kg);处理C、D、E分别为基础日粮+100、200、300mg/kg粉剂丁酸钠;处理F、G、H分别为基础日粮+100、200、300mg/kg包膜丁酸钠;处理Ⅰ为内源组。收集饲料和排泄物样品进行干物质、粗蛋白质、中性洗涤纤维和代谢能的测定。研究结果表明:与对照组相比,两种剂型丁酸钠能够提高肉仔鸡干物质、粗蛋白质、中性洗涤纤维和总能的表观代谢率和真代谢率,剂量达200mg/kg和300mg/kg时可起到部分替代杆菌肽锌和硫酸粘杆菌素的作用。肉仔鸡的表观和真实代谢率随着丁酸钠添加水平的增加而提高,包膜丁酸钠的作用效果优于粉剂丁酸钠。本试验研究范围内,推荐肉仔鸡日粮生产中的最适添加量为200mg/kg包膜或粉剂丁酸钠。     

Population pharmacokinetics of pyrazinamide in elephants

This study was undertaken to characterize the population pharmacokinetics (PK), therapeutic dose, and preferred route of administration for pyrazinamide (PZA) in elephants. Twenty-three African (Loxodonta africana) and Asian (Elephas maximus) elephants infected with or in contact with others culture positive for Mycobacterium tuberculosis were dosed under treatment conditions. PZA was dosed daily at 20-30 mg/kg via oral (fasting or nonfasting state) or rectal (enema or suppository) administration. Blood samples were collected 0-24 h postdose. Population PK was estimated using nonlinear mixed effect modeling. Drug absorption was rapid with T(max) at or before 2 h regardless of the method of drug administration. C(max) at a mean dose of 25.6 (+/-4.6) mg/kg was 19.6 (+/-9.5 microg/mL) for PZA given orally under fasting conditions. Under nonfasting conditions at a mean dose of 26.1 +/- 4.2 mg/kg, C(max) was 25% (4.87 +/- 4.89 microg/mL) and area under concentration curve (AUC) was 30% of the values observed under fasting conditions. Mean rectal dose of 32.6 +/- 15.2 mg/kg yielded C(max) of 12.3 +/- 6.3 microg/mL, but comparable AUC to PZA administered orally while fasting. Both oral and rectal administration of PZA appeared to be acceptable and oral dosing is preferred because of the higher C(max) and lower inter-subject variability. A starting dose of 30 mg/kg is recommended with drug monitoring between 1 and 2 h postdose. Higher doses may be required if the achieved C(max) values are below the recommended 20-50 microg/mL range.     

抗菌肽对肉鸡外周血T淋巴细胞转化的影响

将420只7日龄AA肉雏鸡随机分为7组,在其日粮中分别添加300mg/kg、600mg/kg两个浓度的抗菌肽粗提品,分不同饲养阶段添加到肉鸡日粮中,同时设抗生素组和空白对照组于28日龄早晨空腹翅静脉采抗凝血,分离淋巴细胞,分别用ConA、抗菌肽刺激,MTT法检测T淋巴细胞转化情况。结果表明,抗菌肽能够促进肉鸡外周血淋巴细胞增殖转化,且因添加日龄不同效果有所差异。     

丁酸钠对肉鸡小肠黏膜免疫相关细胞的影响

本试验通过日粮中添加丁酸钠研究其对肉鸡小肠黏膜免疫相关细胞的影响.将32只1日龄健康AA肉鸡随机分为4个处理组:A组(对照组:基础日粮)、B组(丁酸钠组:基础日粮 500mg/kg丁酸钠)、C组(丁酸钠 芽孢杆菌组:基础日粮 100 mg/kg丁酸钠 200 mg/kg芽孢杆菌)和D组(丁酸钠 酶制剂组:基础日粮 100 mg/kg丁酸钠 500 mg/kg酶制剂).试验7周后,采用组织学技术研究肉鸡小肠黏膜免疫相关细胞的分布变化.结果显示:(1)与对照组比较,小肠肥大细胞、上皮内淋巴细胞及杯状细胞的形态无明显变化,肥大细胞多存在于肠腺周围和肠绒毛固有层,(2)各试验组的小肠肥大细胞、上皮内淋巴细胞及杯状细胞数均显著高于对照组(P<0.05);(3)各试验组和对照组小肠肥大细胞和上皮内淋巴细胞数均从前向后逐渐减少,十二指肠的肥大细胞最多,空肠的次之,回肠的较少;杯状细胞数则与之相反.由此可知,3种添加剂可不同程度地改善肉鸡小肠黏膜结构,且将丁酸钠分别与芽孢杆菌和酶制剂混合饲喂,效果在一定程度上好于单独饲喂丁酸钠.     

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in goats given enrofloxacin alone and in combination with probenecid.

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats given enrofloxacin alone or in combination with probenecid. Enrofloxacin was administered i.m. at a dosage of 5 mg x kg(-1) alone or in conjunction with probenecid (40 mg x kg(-1), i.v.). Blood samples were drawn from the jugular vein at predetermined time intervals after drug injection. Plasma was separated and analysed simultaneously for enrofloxacin and ciprofloxacin by reverse-phase high performance liquid chromatography. The plasma concentration-time data for both enrofloxacin and ciprofloxacin were best described by a one-compartment open pharmacokinetic model. The elimination half-life (t(1/2beta)), area under the plasma concentration-time curve (AUC), volume of distribution (V(d(area))), mean residence time (MRT) and total systemic clearance (Cl(B)) were 1.39 h, 7.82 microg x h x mL, 1.52 L x kg(-1), 2.37 h and 802.9 mL x h(-1) x kg(-1), respectively. Enrofloxacin was metabolized to ciprofloxacin in goats and the ratio between the AUCs of ciprofloxacin and enrofloxacin was 0.34. The t(1/2beta), AUC and MRT of ciprofloxacin were 1.82 h, 2.55 microg x h x mL and 3.59 h, respectively. Following combined administration of probenecid and enrofloxacin in goats, the sum of concentrations of enrofloxacin and ciprofloxacin levels > or = 0.1 microg x mL(-1) persisted in plasma up to 12 h.Co-administration of probenecid did not affect the t(1/2beta), AUC, V(d (area)) and Cl(B) of enrofloxacin, whereas the values of t(1/2beta) (3.85 h), AUC (6.29 microg x h x mL), MRT (7.34 h) and metabolite ratio (0.86) of ciprofloxacin were significantly increased. The sum of both enrofloxacin and ciprofloxacin levels was > or = 0.1 microg x mL(-1) and was maintained in plasma up to 8 h in goats after i.m. administration of enrofloxacin alone. These data indicate that a 12 h dosing regime may be appropriate for use in goats.     

植物乳杆菌发酵培养物对单增李斯特菌感染肉鸡的治疗效果及机制

本试验研究了植物乳杆菌发酵培养物对单增李斯特菌感染肉仔鸡的生产性能、氧化反应及促分裂原活化蛋白激酶（MAPK）信号通路的影响,旨在探讨植物乳杆菌发酵培养物对单增李斯特菌感染肉鸡的治疗效果及机制。选择1日龄AA公雏480只,随机分为4组,每组6个重复,每个重复20只鸡。对照组和感染组饲喂基础日粮,抗生素组、乳杆菌培养物组在基础日粮中分别添加40 mg/kg盐酸恩诺沙星和1.6 g/kg灭活植物乳杆菌培养物。5日龄时,感染组、抗生素组和乳杆菌培养物组每只鸡灌服1 mL（10⁵ CFU）单增李斯特菌感染液,对照组灌服无菌株培养液,全程试验期28 d。结果显示,与感染组相比,植物乳杆菌培养物可以显著提高7和28 d肉仔鸡平均日增重、平均日采食量和始末体重（P<0.05）,显著降低肉仔鸡料重比（P<0.05）;显著降低14和28 d肉仔鸡血清和十二指肠黏膜中的二胺氧化酶、丙二醛、蛋白羰基（除14 d十二指肠黏膜外）的含量（P<0.05）;显著降低7和28 d肉仔鸡MAPK3、MAPK10和DUSP6（7 d除外）基因mRNA表达水平（P<0.05）。综上,日粮中添加植物乳杆菌发酵培养物可以提高肉鸡抗氧化性,抑制单增李斯特菌的感染,提高抗菌能力,通过MAPK信号提高抗炎能力。植物乳杆菌发酵培养物对单增李斯特菌感染肉鸡有较好的治疗效果,可以作为替代抗生素的添加剂。     

Pharmacokinetics and endometrial tissue concentrations of enrofloxacin and the metabolite ciprofloxacin after i.v. administration of enrofloxacin to mares

Enrofloxacin was administered i.v. to five adult mares at a dose of 5 mg/kg. After administration, blood and endometrial biopsy samples were collected at regular intervals for 24 h. The plasma and tissue samples were analyzed for enrofloxacin and the metabolite ciprofloxacin by high-pressure liquid chromatography. In plasma, enrofloxacin had a terminal half-life (t(1/2)), volume of distribution (area method), and systemic clearance of 6.7 +/- 2.9 h, 1.9 +/- 0.4 L/kg, and 3.7 +/- 1.4 mL/kg/min, respectively. Ciprofloxacin had a maximum plasma concentration (Cmax) of 0.28 +/- 0.09 microg/mL. In endometrial tissue, the enrofloxacin Cmax was 1.7 +/- 0.5 microg/g, and the t(1/2) was 7.8 +/- 3.7 h. Ciprofloxacin Cmax in tissues was 0.15 +/- 0.04 microg/g and the t(1/2) was 5.2 +/- 2.0 h. The tissue:plasma enrofloxacin concentration ratios (w/w:w/v) were 0.175 +/- 0.08 and 0.47 +/- 0.06 for Cmax and AUC, respectively. For ciprofloxacin, these values were 0.55 +/- 0.13 and 0.58 +/- 0.31, respectively. We concluded that plasma concentrations achieved after 5 mg/kg i.v. are high enough to meet surrogate markers for antibacterial activity (Cmax:MIC ratio, and AUC:MIC ratio) considered effective for most susceptible gram-negative bacteria. Endometrial tissue concentrations taken from the mares after dosing showed that enrofloxacin and ciprofloxacin both penetrate this tissue adequately after systemic administration and would attain concentrations high enough in the tissue fluids to treat infections of the endometrium caused by susceptible bacteria.     

动态氨基酸供给对肉鸡生长性能、屠宰性能、营养物质采食量及肠道发育的影响

本试验旨在根据肉鸡氨基酸需要模型,研究细分饲粮氨基酸供给对肉鸡生长性能、屠宰性能、营养物质采食量及肠道发育的影响。选取1日龄爱拔益加(AA)肉公鸡192只,随机分为4个组,分别为A组(2阶段)、B组(3阶段)、C组(6阶段)和D组(12阶段),每组6个重复,每个重复8只鸡,试验期42 d。结果表明:1)A组肉鸡平均日增重(ADG)显著高于B、C和D组(P0.05)。A、B、C组之间肉鸡平均日采食量(ADFI)差异不显著(P0.05),均显著高于D组(P0.05)。A组肉鸡料重比(F/G)显著低于B、C和D组(P0.05)。2)B组肉鸡屠宰率显著高于A、C和D组(P0.05)。B组肉鸡全净膛率显著高于C和D组(P0.05),与A组差异不显著(P0.05)。A组肉鸡胸肌率显著高于B、C和D组(P0.05)。A组肉鸡腹脂率显著低于B、C和D组(P0.05)。3)D组肉鸡代谢能采食量显著低于A、B和C组(P0.05)。A组肉鸡粗蛋白质及赖氨酸采食量显著高于B、C和D组(P0.05),B、C组肉鸡粗蛋白质及赖氨酸采食量显著高于D组(P0.05)。A组肉鸡蛋氨酸采食量显著高于B和D组(P0.05)。A组肉鸡含硫氨基酸采食量显著高于B和D组(P0.05)。D组肉鸡苏氨酸采食量显著低于A和C组(P0.05)。4)A组肉鸡十二指肠绒毛高度、绒毛高度/隐窝深度(V/C)值显著高于B、C和D组(P0.05)。各组肉鸡空肠、回肠绒毛高度、隐窝深度及V/C值差异不显著(P0.05)。5)42日龄,A组肉鸡体重显著高于B、C和D组(P0.05),B和C组肉鸡体重显著高于D组(P0.05)。B、C和D组肉鸡单位增重成本与A组相比差异不显著(P0.05)。综上,2阶段饲喂能够促进肉鸡十二指肠发育,提高肉鸡营养物质采食量。综合生长性能、屠宰性能及单位增重成本考虑,建议采用2阶段肉鸡饲喂方式。     

乳酸恩诺沙星对小鼠的急性毒性试验

研究了乳酸恩诺沙星对小鼠的急性毒性,用寇氏法计算实验小鼠的半数致死量(LD50)和95%置信限。结果表明,乳酸恩诺沙星对小白鼠灌胃染毒及腹腔注射染毒的LD50分别为3579mg/kg和571.3mg/kg,其95%可信限分别为3011～4255mg/kg和498.3～655.1mg/kg。研究提示,乳酸恩诺沙星属低毒物质,其可溶性粉能用于开展药效试验。     

Distribution of enrofloxacin and its active metabolite, using an in vivo ultrafiltration sampling technique after the injection of enrofloxacin to pigs

The objective of this study was to determine the pharmacokinetics (PK) of enrofloxacin in pigs and compare to the tissue interstitial fluid (ISF). Six healthy, young pigs were administered 7.5 mg/kg enrofloxacin subcutaneously (SC). Blood and ISF samples were collected from preplaced intravenous catheters and ultrafiltration sampling probes placed in three different tissue sites (intramuscular, subcutaneous, and intrapleural). Enrofloxacin concentrations were measured using high-pressure liquid chromatography with fluorescence detection, PK parameters were analyzed using a one-compartment model, and protein binding was determined using a microcentrifugation system. Concentrations of the active metabolite ciprofloxacin were negligible. The mean ± SD enrofloxacin plasma half-life, volume of distribution, clearance, and peak concentration were 26.6 ± 6.2 h (harmonic mean), 6.4 ± 1.2 L/kg, 0.18 ± 0.08 L/kg/h, and 1.1 ± 0.3 μg/mL, respectively. The half-life of enrofloxacin from the tissues was 23.6 h, and the maximum concentration was 1.26 μg/mL. Tissue penetration, as measured by a ratio of area-under-the-curve (AUC), was 139% (± 69%). Plasma protein binding was 31.1% and 37.13% for high and low concentrations, respectively. This study demonstrated that the concentration of biologically active enrofloxacin in tissues exceeds the concentration predicted by the unbound fraction of enrofloxacin in pig plasma. At a dose of 7.5 mg/kg SC, the high tissue concentrations and long half-life produce an AUC/MIC ratio sufficient for the pathogens that cause respiratory infections in pigs.