Pharmacokinetics of Flunixin Meglumine After Intravenous and Intramuscular Administration in Pigs

Pharmacokinetics of flunixin meglumine （FM） was investigated in 14 healthy pigs following single intravenous （i.v.） and intramuscular （i.m.） administration of the drug at the dosage of 2.2 and 1.1 mg kg-1. Blood samples were collected at different intervals after administration, and concentrations of FM were determined by HPLC method with a limit of detection of 0.1μg mL-1. The FM concentration-time data were fitted to a two-compartment open model after single i.v. dosing in pigs. The main pharmacokinetic parameters were as follows： tl/2a, 0.49 ± 0.03 and 0.58±0.07 h; tl/2β, 6.28±0.13 and 7.37 ±0.59 h; V/F, 0.01 ±0.001 and 0.01 ±0.002 L kg-1; CL, 0.01 ± 0.002 and 0.01 ± 0.002 L h-l; AUC, 237.73 ± 52.46 and 147.71 ± 36.76μg h-1 mL-1. The drug concentration-time data were fitted to a two-compartment model with first-order absorption after single i.m. administration in pigs. The main pharmacokinetic parameters were as follows： t1/2α, 0.90± 0.07 and 0.86±0.10 h; t1/2β, 8.79±0.85 and 9.60±0.10 h; V/F, 0.02±0.004 and 0.02±0.003 L kg-1; CL, 0.01±0.002 and 0.01 ±0.003 L h-l; AUC, 174.63 ± 45.84 and 112.42 ± 31.19 pg h-1 mL 1. The results of the present study showed that FM was rapidly absorbed, extensively distributed, and slowly eliminated in pigs. The drug was completely absorbed after single i.m. administration and a good bioavailability in pigs.     

Amoxicillin—current use in swine medicine

Amoxicillin has become a major antimicrobial substance in pig medicine for the treatment and control of severe, systemic infections such as Streptococcus suis. The minimum inhibitory concentration 90% (MIC 90) is 0.06 μg amoxicillin/ml, and the proposed epidemiological cut‐off value (ECOFF) is 0.5 μg/ml, giving only 0.7% of isolates above the ECOFF or of reduced susceptibility. Clinical breakpoints have not been set for amoxicillin against porcine pathogens yet, hence the use of ECOFFs. It has also been successfully used for bacterial respiratory infections caused by Actinobacillus pleuropneumoniae and Pasteurella multocida. The ECOFF for amoxicillin against A. pleuropneumoniae is also 0.5 μg/ml demonstrating only a reduced susceptibility in 11.3% of isolates. Similarly, P. multocida had an ECOFF of 1.0 μg/ml and a reduced susceptibility in only 2.6% of isolates. This reduced susceptibility disappears when combined with the beta‐lactamase inhibitor, clavulanic acid, demonstrating that it is primarily associated with beta‐lactamase production. In contrast, amoxicillin is active against Escherichia coli and Salmonella species but using ECOFFs of 8.0 and 4.0 μg/ml, respectively, reduced susceptibility can be seen in 70.9% and 67.7% of isolates. These high levels of reduced susceptibility are primarily due to beta‐lactamase production also, and most of this resistance can be overcome by the combination of amoxicillin with clavulanic acid. Currently, amoxicillin alone is considered an extremely valuable antimicrobial in both human and animal medicine and remains in the critically important category of antibiotics alongside the fluoroquinolones and macrolides by the World Health Organization as well as the third‐ and fourth‐generation cephalosporins, but these cephalosporins show marked resistance to basic beta‐lactamase production and are only destroyed by the extended‐spectrum beta‐lactamases. Amoxicillin alone and in combination with clavulanic acid are currently classed together in Category 2 in the European Union. By reviewing the pharmacodynamic data and comparing this with pharmacokinetic data from healthy and infected animals and clinical trial data, it can be seen that the product has a good efficacy against S. suis and A. pleuropneumoniae, in spite of usage over many years. However, it may be much less efficacious on its own against E. coli, due to reduced susceptibility and resistance associated with beta‐lactamase production, which is largely overcome by the use of clavulanic acid. It is felt that this differentiation may be useful in future classification of amoxicillin alone, in comparison with its combined use with clavulanic acid and thereby preserve the use of the more critically important antibiotics in veterinary medicine and reducing the risk of their resistance being transmitted to human.     

盐酸土霉素在奥尼罗非鱼体内的药代动力学及残留研究

在水温(25±2)℃条件下,以15 mg/kg鱼体重的剂量给奥尼罗非鱼单次口灌盐酸土霉素,采用高效液相色谱法测定血浆和肌肉组织中的药物浓度,研究盐酸土霉素在奥尼罗非鱼体内的代谢及消除规律。结果显示:血药时间数据符合一级吸收二室开放模型,半衰期(T1/2Ka、T1/2α、T1/2β)分别为4.79、4.10、45.20 h,最大血药浓度为1.50μg/m L,达峰时间为7.30 h,药时曲线下面积(AUC)为42.35μg·h/m L。肌肉作为可食性组织,选取肌肉组织作为残留检测的靶组织,以0.1 mg/kg为最高残留限量,在本试验条件下,建议休药期不低于10 d。     

三氧化二砷在鸡组织内的代谢动力学研究

为了解砷在不同组织中的代谢及分布特点,试验采用新银盐法研究三氧化二砷在正常鸡组织中的代谢动力学过程。结果表明,30日龄鸡腹腔注射三氧化二砷注射液3 mg.kg-1后,根据药代动力学参数,得出各组织内三氧化二砷代谢的动力学方程,肝脏、肾脏符合一级吸收二室开放模型,胸肌符合一级吸收一室开放模型。     

氟苯尼考在红笛鲷体内的药代动力学研究

为研究氟苯尼考在红笛鲷体内的药代动力学特征,在水温(20±2)℃条件下,氟苯尼考以10 mg/kg单剂量腹注和口灌健康红笛鲷(Lutjanus sanguineus),采用HPLC-MS/MS测定组织中的药物浓度,数据用DAS3.0软件分析。结果显示,两种给药方式下红笛鲷血浆药时数据均符合一级吸收二室模型;腹注给药后血浆、肝脏、肾脏和肌肉的峰浓度(C_(max))分别为10.62μg/m L、8.36、22.57和4.76μg/g,达峰时间(T_(max))分别为1.2、1.0、1.0和6.0 h,消除半衰期(t_(1/2β))分别为29.76、17.84、17.23和19.48 h;口灌给药后血浆、肝脏、肾脏和肌肉的C_(max)分别为2.35μg/m L、1.45μg/g、4.06μg/g和1.73μg/g,T_(max)分别为2.69、1.5、1.5和4.0 h,t_(1/2β)分别为40.59、12.29、37.78和47.34 h。结果表明,腹注给药方式下氟苯尼考在红笛鲷体内的吸收快于口灌给药,在血浆和肝脏中的消除快于口灌给药,在肌肉和肾脏中的消除则慢于口灌给药。研究结果为氟苯尼考在临床上的合理应用提供了科学依据。     

Some Pharmacokinetic Parameters of Oxfendazole in Sheep

Soraci, A.L., Mestorino, N. and Errecalde, J.O., 1997. Some pharmacokinetic parameters of oxfendazole in sheep. Veterinary Research Communications, 21 (4), 283-287     

猪生长激素(PST)脂质体代谢动力学的研究

在猪体内注射脂质体 ,研究其在体内的药物动力学 ,分析其血浆中生长激素浓度随时间的变化曲线 ,确定其释药模型为单室模型 ,求出各项动力学参数 ,结果为PST脂质体的缓释效果显著 ,缓释时间长达7天以上