盐酸沙拉沙星(sarafloxacin)在鸡体内的药动学和生物利用度

2组健康艾维因肉鸡各 8只 ,体重 (1.6 6± 0 .11) kg,研究了对其单剂量 (10 mg/kg,以沙拉沙星碱计 )静注和口服盐酸沙拉沙星后的药动学及其生物利用度 ,用高效液相色谱法测定血清中沙拉沙星的浓度。结果表明 :静注盐酸沙拉沙星溶液后 ,血清药物浓度经时过程符合无吸收因素二室模型 ,其消除半衰期 (t1 / 2β)、总体清除率 (CLB)、表观分布容积 (Vd)和药时曲线下面积 (AU C)分别为 (2 .6 78± 0 .5 0 6 ) h、(1.339± 0 .35 1) L/kg· h、(5 .15 9± 1.5 5 4) L/kg和(7.85 3± 1.731) mg/L· h;口服盐酸沙拉沙星片后 ,药时数据呈有吸收因素一室模型 ,其吸收和消除半衰期 (t1 / 2 ka,t1 / 2 ke)、血清峰浓度 (Cmax)、达峰时间 (Tmax)和药时曲线下面积 (AUC)分别为 (0 .2 87± 0 .117) h、(5 .381± 1.44 6 ) h、(0 .478± 0 .196 ) mg/L、(1.2 2 9± 0 .439) h和 (4 .0 6 0± 1.178) m g/L· h,生物利用度为 (5 1.70± 15 .0 0 ) %。     

黄牛静注、肌注和内服吡喹酮的药动学与生物利用度

6头成年健康黄牛按10 mg/kg剂量单次快速静注吡喹酮,另6头成年健康黄牛根据交叉试验设计法按10 mg/kg剂量单次肌注、30 mg/kg剂量内服吡喹酮进行药动学与生物利用度试验.利用高效液相色谱法测定血浆中吡喹酮原药的质量浓度,其检测限为25μg/L.房室模型分析表明,静注给药后的药时数据符合无吸收二室开放模型,其分布半衰期(t1/2a)、消除半衰期(t1/2β)、表观分布容积(Vd)、总体清除率(ClB)、药时曲线下面积(AUC)分别为(0.25±0.03)h、(1.28±0.20)h、(2.11±0.38)L/kg、(1.14±0.10)L/(kg·h)和(8.79±0.74)mg/(L·h).肌注的药时数据符合有吸收一室开放模型,主要药动学参数吸收半衰期(t 1/2ka)、消除半衰期(t1/2ke)、药时曲线下面积(AUC)、达峰时间(tmax)、峰浓度(Gmax)和生物利用度(F)分别为(0.40±0.17)h、(4.65±0.91) h、(6.85±1.02)mg/(L·h)、(1.33±0.52)h、(0.83±0.08)mg/L和77.93%.内服给药后符合有吸收一室开放模型,吸收不规则,其药动学参数t 1/2ka、t1/2ke、AUC、tmax、Cmax和F分别为(1.08±0.13)h、(6.81±1.26)h、(8.51±1.78)mg/(L·     

Biovailability of ivermectin administered orally to dogs

The bioavailability of three formulations of ivermectin was determined following oral administration to dogs. The average peak plasma level (C _max) of ivermectin administered in the standard tablet formulation at 6 and 100 µg/kg of body weight was 2.97 and 44.31 ng/g, respectively. This suggest dose-dependent pharmacokinetics.C _max and total ivermectin bioavailability, as assessed from the area under the plasma curve (AUC), were similar between two tablet formulations of ivermectin administered at 100 µg/kg. Furthermore,C _max was similar following administration of radiolabelled ivermectin at 6 µg/kg in either a beef-based chewable formulation or in the standard tablet formulation.     

Pharmacokinetic profiles of the two major active metabolites of metamizole (dipyrone) in cats following three different routes of administration

This study was performed to determine pharmacokinetic profiles of the two active metabolites of the analgesic drug metamizole (dipyrone , MET), 4‐methylaminoantipyrine (MAA), and 4‐aminoantipyrine (AA), after intravenous (i.v., intramuscular (i.m.), and oral (p.o.) administration in cats. Six healthy mixed‐breed cats were administered MET (25 mg/kg) by i.v., i.m., or p.o. routes in a crossover design. Adverse clinical signs, namely salivation and vomiting, were detected in all groups (i.v. 67%, i.m. 34%, and p.o. 15%). The mean maximal plasma concentration of MAA for i.v., i.m., and p.o. administrations was 148.63 ± 106.64, 18.74 ± 4.97, and 20.59 ± 15.29 μg/ml, respectively, with about 7 hr of half‐life in all routes. Among the administration routes, the area under the plasma concentration curve (AUC) value was the lowest after i.m. administration and the AUC_EV/i.v. ratio was higher in p.o. than the i.m. administration without statistical significance. The plasma concentration of AA was detectable up to 24 hr, and the mean plasma concentrations were smaller than MAA. The present results suggest that MET is converted into the active metabolites in cats as in humans. Further pharmacodynamics and safety studies should be performed before any clinical use.     

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.     

Comparison of the pharmacokinetic profiles of two different amphotericin B formulations in healthy dogs

This study was conducted to compare the pharmacokinetic profiles of conventional (Fungizone^®) and liposomal amphotericin B (AmBisome^®) formulations in order to predict their therapeutic properties, and evaluate their potential differences in veterinary treatment. For this purpose, twelve healthy mixed breed dogs received both drugs at a dose of 0.6 mg/kg by intravenous infusion over a 4‐min period in a total volume of 40 ml. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72 and 96 hr after dosing, and concentrations of drug in plasma were determined by high‐performance liquid chromatography (HPLC). Pharmacokinetics was described by a two‐compartment model. Although both formulations were administered at the same doses (0.6 mg/kg), the plasma pharmacokinetics of liposomal amphotericin B differed significantly from those of amphotericin B deoxycholate in healthy dogs (p < .05). Liposomal amphotericin B showed markedly higher peak plasma concentrations (approximately ninefold greater) and higher area under the plasma concentration curve values (approximately 14‐fold higher) compared to conventional formulation. It is concluded that AmBisome^® reached higher plasma concentration and lower distribution volume and had a longer half‐life compared to Fungizone^®, and therefore, AmBisome^® is reported to be an appropriate and effective choice for the treatment of systemic mycotic infections in dogs.     

The influence of rapid growth on sodium salicylate pharmacokinetics in male turkeys

The aim of this study was to assess the influence of growth on the pharmacokinetics of sodium salicylate (SS) in male turkeys. SS was administered intravenously at a dose of 50 mg/kg. Plasma drug concentrations were assessed by high‐performance liquid chromatography, and pharmacokinetic parameters were calculated by noncompartmental analysis. As the age increased from 6 to 13 weeks (body weight increase from 2.35 to 9.43 kg), median body clearance decreased from 1.34 to 0.87 ml/min/kg. This caused a significant increase in the median mean residence time from 3.42 to 4.44 hr. Elimination phase proved to be biphasic and two elimination half‐lives (T_1/2el) were distinguished. Whereas T_1/2el1 was found to increase with age by 128%, T_1/2el2 represented a later but faster and less age‐dependent phase of elimination (increase by 56% in the respective groups). Volume of distribution decreased with age. These effects may lead to different therapeutic response to SS in turkeys of different age and body weights.     

泰地罗新注射液在藏香猪体内的药物动力学研究

为研究泰地罗新在藏香猪体内的药物动力学特征,了解其在藏香猪体内的吸收、分布、转化及排泄规律,为泰地罗新注射液的临床合理用药提供参考。本试验选取8头藏香猪,泰地罗新单剂量注射给药,不同时间点采集藏香猪血液,利用高效液相色谱法测定血浆中药物浓度。结果表明：泰地罗新注射给药(4 mg/kg.bw)后,泰地罗新在藏香猪体内的药-时曲线符合有吸收三室开放模型,其主要药动学参数为：Tmax为0.457±0.143h,Cmax为0.759±0.192 μg/mL,t1/2为120.518±10.181h,AUC为22.224±2.641μg.h/mL。表明泰地罗新注射给药后,在藏香猪体内吸收迅速,消除较为缓慢。     

Pharmacokinetics of articaine hydrochloride and its metabolite articainic acid after subcutaneous administration in red deer (Cervus elaphus)

AIM: To develop and validate a simple and sensitive method using liquid chromatography-mass spectrometry (LC-MS) for quantification of articaine, and its major metabolite articainic acid, in plasma of red deer (Cervus elaphus), and to investigate the pharmacokinetics of articaine hydrochloride and articainic acid in red deer following S/C administration of articaine hydrochloride as a complete ring block around the antler pedicle.

METHODS: The LC-MS method was validated by determining linearity, sensitivity, recovery, carry-over and repeatability. Articaine hydrochloride (40?mg/mL) was administered S/C to six healthy male red deer, at a dose of 1?mL/cm of pedicle circumference, as a complete ring block around the base of each antler. Blood samples were collected at various times over the following 12 hours. Concentrations in plasma of articaine and articainic acid were quantified using the validated LC-MS method. Pharmacokinetic parameters of articaine and articainic acid were estimated using non-compartmental analysis.

RESULTS: Calibration curves were linear for both articaine and articainic acid. The limits of quantifications for articaine and articainic acid were 5 and 10?ng/mL, respectively. Extraction recoveries were >72% for articaine and >68% for articainic acid. After S/C administration as a ring block around the base of each antler, mean maximum concentrations in plasma (C_max) of articaine were 1,013.9 (SD 510.1) ng/mL, detected at 0.17 (SD 0.00) hours, and the C_max for articainic acid was 762.6 (SD 95.4) ng/mL at 0.50 (SD 0.00) hours. The elimination half-lives of articaine hydrochloride and articainic acid were 1.12 (SD 0.17) and 0.90 (SD 0.07) hours, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE: The LC-MS method used for the quantification of articaine and its metabolite articainic acid in the plasma of red deer was simple, accurate and sensitive. Articaine hydrochloride was rapidly absorbed, hydrolysed to its inactive metabolite articainic acid, and eliminated following S/C administration as a ring block in red deer. These favourable pharmacokinetic properties suggest that articaine hydrochloride should be tested for efficacy as a local anaesthetic in red deer for removal of velvet antlers. Further studies to evaluate the safety and residues of articaine hydrochloride and articainic acid are required before articaine can be recommended for use as a local anaesthetic for this purpose.     

Pharmacokinetics of carbetocin,a long‐acting oxytocin analogue,following intravenous administration in horses

Reason for performing study: Current therapy protocols to treat persistent post mating endometritis and retained fetal membranes in mares typically include the administration of ecbolic drugs. Evaluation of the pharmacokinetics and tolerability of carbetocin, a long‐acting oxytocin analogue, after i.v. administration is required. Objectives: To determine the pharmacokinetic parameters (principally half‐life) of carbetocin in horses. Methods: Five mature mares and one gelding received 0.175 mg carbetocin i.v. All animals were monitored periodically throughout the study for elevation in rectal temperature, heart rate, respiratory rate and signs of pain or discomfort. Plasma samples were collected for determination of carbetocin concentrations by radioimmunoassay. Results: Administration of carbetocin was well tolerated by all horses and its half‐life was 17.2 min. Conclusions: The half‐life of carbetocin is greater than that previously reported for oxytocin (6.8 min). Potential relevance: Carbetocin is an attractive alternative to oxytocin therapy in broodmare management.