Pharmacokinetic profile of amoxicillin and its glucuronide-like metabolite when administered subcutaneously to koalas (Phascolarctos cinereus)

Amoxicillin was administered as a single subcutaneous injection at 12.5 mg/kg to four koalas and changes in amoxicillin plasma concentrations over 24 hr were quantified. Amoxicillin had a relatively low average ± SD maximum plasma concentration (C_max) of 1.72 ± 0.47 µg/ml; at an average ± SD time to reach C_max (T_max) of 2.25 ± 1.26 hr, and an elimination half-life of 4.38 ± 2.40 hr. The pharmacokinetic profile indicated relatively poor subcutaneous absorption. A metabolite was also identified, likely associated with glucuronic acid conjugation. Bacterial growth inhibition assays demonstrated that all plasma samples other than t = 0 hr, inhibited the growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 to some extent. Calculated pharmacokinetic indices were used to predict whether this dose could attain a plasma concentration to inhibit some susceptible Gram-negative and Gram-positive pathogens. It was predicted that a twice daily dose of 12.5 mg/kg would be efficacious to inhibit susceptible bacteria with an amoxicillin minimum inhibitory concentration (MIC) ≤ 0.75 µg/ml such as susceptible Bordetella bronchiseptica, E. coli, Staphylococcus spp. and Streptococcus spp. pathogens.     

Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part I: Cattle and swine

Physiologically based pharmacokinetic (PBPK) models for chemicals in food animals are a useful tool in estimating chemical tissue residues and withdrawal intervals. Physiological parameters such as organ weights and blood flows are an important component of a PBPK model. The objective of this study was to compile PBPK-related physiological parameter data in food animals, including cattle and swine. Comprehensive literature searches were performed in PubMed, Google Scholar, ScienceDirect, and ProQuest. Relevant literature was reviewed and tables of relevant parameters such as relative organ weights (% of body weight) and relative blood flows (% of cardiac output) were compiled for different production classes of cattle and swine. The mean and standard deviation of each parameter were calculated to characterize their variability and uncertainty and to allow investigators to conduct population PBPK analysis via Monte Carlo simulations. Regression equations using weight or age were created for parameters having sufficient data. These compiled data provide a comprehensive physiological parameter database for developing PBPK models of chemicals in cattle and swine to support animal-derived food safety assessment. This work also provides a basis to compile data in other food animal species, including goats, sheep, chickens, and turkeys.     

白鸡屎藤挥发油抗肠炎沙门菌及其内毒素的作用

雏鸡肠炎沙门菌病是肠炎沙门菌及其内毒素共同作用的结果。为了研究白鸡屎藤挥发油抗肠炎沙门菌及其内毒素的作用,本试验测定了白鸡屎藤挥发油抗肠炎沙门菌的效果,进一步提取了肠炎沙门菌内毒素并测试了白鸡屎藤挥发油对肠炎沙门菌内毒素的体外灭活作用和对肠炎沙门菌内毒素致热的解热作用,同时本试验还对白鸡屎藤挥发油进行了定性定量分析并测试了白鸡屎藤挥发油及其主要药理活性成分的药动学特征。结果显示,白鸡屎藤挥发油包括丁香酚、樟脑、龙脑、水杨酸甲酯等活性成分,在中剂量（100mL／L）、高剂量（150mL／L）均表现出较强的体外抑菌效果,25mL／L以上浓度即可表现出较强的灭活内毒素作用,并且2～4h大部活性成分进入血液循环,表现出显著的解热作用。结果表明,白鸡屎藤挥发油具有一定的抗菌、抗内毒素和解热作用,可以用于雏鸡肠炎沙门菌感染性发热病的治疗。     

复方盐酸头孢噻呋混悬剂的药代动力学研究

利用药物动力学的方法考察复方盐酸头孢噻呋混悬剂是否具备缓释长效的特点,同时研究鱼腥草油对头孢噻呋药代动力学的影响。36只SPF大鼠随机平均分成三组:A组单剂量注射复方盐酸头孢噻呋混悬剂,B组单剂量注射盐酸头孢噻呋混悬剂,C组单剂量注射头孢噻呋钠粉针;三组注射剂量均为50 mg/(kg.bw)。采用反相高效液相色谱内标法测定血浆药物浓度,并以DAS2.0药动学程序和SPSS(11.0)统计软件对所得数据进行分析。A、B、C组药时数据均符合一级吸收二室模型(权重=1/cc),主要动力学参数如下:A组:T1/2Ka=(1.253±0.100)h,Tpeak=(2.000±0.000)h,Cmax=(35.203±5.732)mg/L,AUC=(229.51±18.278)mg.h/L;B组:T1/2Ka=(0.341±0.090)h,Tpeak=(1.000±0.000)h,Cmax=(43.919±1.51)mg/L,AUC=(188.488±9.611)mg.h/L;C组:T1/2Ka=(0.044±0.012)h,Tpeak=(0.167±0.000)h,Cmax=(159.091±19.971)mg/L,AUC=(128.554±6.625)mg.h/L。实验数据表明,复方盐酸头孢噻呋混悬剂肌肉注射后,其药物动力学特征表现为吸收缓慢,血药浓度平稳,消除半衰期延长,生物利用度高等特点,在临床上注射1次,连用3 d,可以维持有效血液浓度。     

兽用喹诺酮类药物--奥比沙星

本文简述了奥比沙星的体外抗菌活性、药代动力学参数、用药剂量规定、生物利用度及休药期等，并与恩诺沙星和单诺沙星作了比较。     

口服喹烯酮代谢动力学研究

依据本实验建立的高效液相色谱法，测定了口服大剂量喹烯酮的肉鸡、仔猪血液浓度。结果表明：喹烯酮口服后，作用于消化道，不易被机体吸收，主要以原药形式排出体外，所以喹烯酮在机体内的残留极少。     

An integrated experimental and physiologically based pharmacokinetic modeling study of penicillin G in heavy sows

Penicillin G is widely used in food‐producing animals at extralabel doses and is one of the most frequently identified violative drug residues in animal‐derived food products. In this study, the plasma pharmacokinetics and tissue residue depletion of penicillin G in heavy sows after repeated intramuscular administrations at label (6.5 mg/kg) and 5 × label (32.5 mg/kg) doses were determined. Plasma, urine, and environmental samples were tested as potential antemortem markers for penicillin G residues. The collected new data and other available data from the literature were used to develop a population physiologically based pharmacokinetic (PBPK) model for penicillin G in heavy sows. The results showed that antemortem testing of urine provided potential correlation with tissue residue levels. Based on the United States Department of Agriculture Food Safety and Inspection Service action limit of 25 ng/g, the model estimated a withdrawal interval of 38 days for penicillin G in heavy sows after 3 repeated intramuscular injections at 5 × label dose. This study improves our understanding of penicillin G pharmacokinetics and tissue residue depletion in heavy sows and provides a tool to predict proper withdrawal intervals after extralabel use of penicillin G in heavy sows, thereby helping safety assessment of sow‐derived meat products.     

Investigation of pharmacokinetic interaction between ivermectin and praziquantel after oral administration in healthy dogs

The purpose of this study was to determine the pharmacokinetic interaction between ivermectin (0.4 mg/kg) and praziquantel (10 mg/kg) administered either alone or co‐administered to dogs after oral treatment. Twelve healthy cross‐bred dogs (weighing 18–21 kg, aged 1–3 years) were allocated randomly into two groups of six dogs (four females, two males) each. In first group, the tablet forms of praziquantel and ivermectin were administered using a crossover design with a 15‐day washout period, respectively. Second group received tablet form of ivermectin plus praziquantel. The plasma concentrations of ivermectin and praziquantel were determined by high‐performance liquid chromatography using a fluorescence and ultraviolet detector, respectively. The pharmacokinetic parameters of ivermectin following oral alone‐administration were as follows: elimination half‐life (t_1/2λz) 110 ± 11.06 hr, area under the plasma concentration–time curve (AUC_0–∞) 7,805 ± 1,768 hr^.ng/ml, maximum concentration (C_max) 137 ± 48.09 ng/ml, and time to reach C_max (T_max) 14.0 ± 4.90 hr. The pharmacokinetic parameters of praziquantel following oral alone‐administration were as follows: t_1/2λz 7.39 ± 3.86 hr, AUC_0–∞ 4,301 ± 1,253 hr^.ng/ml, C_max 897 ± 245 ng/ml, and T_max 5.33 ± 0.82 hr. The pharmacokinetics of ivermectin and praziquantel were not changed, except T_max of praziquantel in the combined group. In conclusion, the combined formulation of ivermectin and praziquantel can be preferred in the treatment and prevention of diseases caused by susceptible parasites in dogs because no pharmacokinetic interaction was determined between them.     

Determination of milk/plasma ratio and milk and plasma pharmacokinetics of amoxicillin after intramuscular administration in lactating cows

This study was conducted to determine the passage ratio of amoxicillin into milk and its pharmacokinetics in milk and plasma after intramuscular administration. Five healthy dairy cows (Holstein, weighing 450–500 kg, aged 2–4 years) were used in this study. They received single intramuscular amoxicillin at a dose of 14 mg/kg body weight. Blood and milk samples were collected prior to drug administration (0); after 15, 30, 45, 60, and 90 min; and 2, 3, 4, 6, 8, 10, and 12 hr after administration. The plasma and milk concentrations of amoxicillin were determined using high‐performance liquid chromatography with ultraviolet detection. The passage ratio of amoxicillin into milk and plasma was determined using both AUC‐based calculation and milk and plasma concentrations at sampling times; it was calculated 0.46 and 0.52, respectively. The terminal half‐life and mean residence time of amoxicillin were 6.05 and 8.60 hr in plasma and 2.62 and 5.35 hr in milk, respectively. The C_max2 levels of amoxicillin in plasma and milk were measured as 1,096 and 457 ng/ml, respectively. It was observed that amoxicillin exhibited a secondary peak in plasma and milk. This study was the first to report on the passage ratio of amoxicillin into milk in lactating cows.