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·     

The distribution and some pharmacokinetic parameters of ivermectin in pigs

Ivermectin was injected subcutaneously into five pigs at the usual dose rate of 300 µg/kg and found to distribute well to all tissues and body fluids which were sampled 24 h post-injection. Ivermectin was detected in the contents and mucus at all levels of the gastrointestinal tract. The drug was excreted in bile, with high concentrations of the drug in the intestines and faeces. High concentrations of ivermectin were measured in skin, ears and ear wax, suggesting that the drug should be effective in the treatment of ectoparasitic infestations, particularly ear mites. The high lipid solubility of the drug may explain the high concentrations found in ear wax and skin. Ivermectin was also detected in the body fluids and tissues of an untreated pig penned with the treated animals. Direct contact appeared to be necessary for transfer of ivermectin from the treated to the untreated pig but coprophagia or urine drinking is a possible explanation.The pharmacokinetics of ivermectin administered subcutaneously at a dose rate of 300 µg/kg to six pigs were studied. There was marked individual variation in the pharmacokinetics of ivermectin. In one pig the area under the plasma concentration-time curve was particularly high. This may reflect individual variation in uptake and excretion of the drug. The mean elimination half-life of the drug was 35.2 h, suggesting that the drug is cleared slowly from pigs with drug detectable in plasma for 6–10 days. This persistence should allow a short period of protection before re-infection with parasites.     

Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site

ObjectiveTo describe the pharmacokinetics and adverse effects of intravenous (IV) and sublingual (SL) buprenorphine in horses, and to determine the effect of sampling site on plasma concentrations after SL administration.Study designRandomized crossover experiment; prospective study.AnimalsEleven healthy adult horses between 6 and 20 years of age and weighing 487–592 kg.MethodsIn the first phase; buprenorphine was administered as a single IV or SL dose (0.006 mg kg^?1) and pharmacokinetic parameters were determined for each route of administration using a noncompartmental model. In the second phase; the jugular and lateral thoracic veins were catheterized for simultaneous venous blood sampling, following a dose of 0.006 mg kg^?1 SL buprenorphine. For both phases, plasma buprenorphine concentrations were measured using ultra-performance liquid chromatography with mass spectrometry. At each sampling period, horses were assessed for behavioral excitement and gastrointestinal motility.ResultsFollowing IV administration, buprenorphine mean ± SD half-life was 5.79 ± 1.09 hours. Systemic clearance (Cl) following IV administration was 6.13 ± 0.86 mL kg^?1 minute^?1 and volume of distribution at steady-state was 3.16 ± 0.65 L kg^?1. Following IV administration, horses showed signs of excitement. Gastrointestinal sounds were decreased following both routes of administration; however, none of the horses exhibited signs of colic. There was a significant discrepancy between plasma buprenorphine concentrations measured in the jugular vein versus the lateral thoracic vein following phase 2, thus pharmacokinetic parameters following SL buprenorphine are not reported.Conclusions and clinical relevanceBuprenorphine has a long plasma half-life and results in plasma concentrations that are consistent with analgesia in other species for up to 4 hours following IV administration of this dose in horses. While buprenorphine is absorbed into the circulation following SL administration, jugular venous sampling gave a false measurement of the quantity absorbed and should not be used to study the uptake from SL administration.     

Pharmacokinetics of topically applied ciprofloxacin in tears of mesocephalic and brachycephalic dogs

OBJECTIVE: To evaluate the pharmacokinetics of ophthalmic ciprofloxacin in the tear film of normal mesocephalic and brachycephalic dogs. ANIMALS STUDIED: Twenty mesocephalic dogs and 15 brachycephalic dogs. PROCEDURES: Thirty-five microliters of ciprofloxacin were placed on the cornea of both eyes of each dog. Five brachycephalic dogs were used twice. A tear-test strip placed in the ventral cul de sac for 30 s was used to obtain samples. The tear film of each eye was sampled once at eight time-points post administration, resulting in five samples at each time-point. Samples were evaluated using high performance liquid chromatography. Data from the two skull types were compared using the unpaired two-tailed t-test. RESULTS: The mean concentration of ciprofloxacin in the tears of mesocephalic dogs was 192.8 +/- 269.97, 140.6 +/- 91.06, 56.60 +/- 28.47, 13.6 +/- 6.3, 43.25 +/- 59.71, 16.6 +/- 10.62, 15.6 +/- 13.16 and 6.25 +/- 9.84 microg/g at 5, 10, 15, 30 min and 1, 2, 4 and 6 h, respectively. The mean concentration of ciprofloxacin in the tears of brachycephalic dogs was 272.6 +/- 106.21, 144.4 +/- 142.32, 131.2 +/- 147.07, 75 +/- 80.07, 40.8 +/- 30.35, 35 +/- 21.98, 52.75 +/- 51.87 and 8.6 +/- 12.10 microg/g at 5, 10, 15, 30 min and 1, 2, 4 and 6 h, respectively. There was no statistical difference in tear concentration at any time-point between skull types. CONCLUSIONS: Topical application of ciprofloxacin resulted in a mean tear concentration of ciprofloxacin that remained above the MIC(90) levels for most pathogenic bacteria for 6 h in normal mesocephalic and brachycephalic dogs.     

Disposition Kinetics of Difloxacin After Intravenous,Intramuscular and Subcutaneous Administration in Calves

The pharmacokinetics of difloxacin (Dicural) was studied in a crossover study using three groups (n = 4) of male and female Friesian calves after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administrations of 5 mg/kg body weight. Drug concentration in plasma was determined by high-performance liquid chromatography using fluorescence detection. The plasma concentration–time data following i.v. administration were best fitted to a two-compartment open model and those following i.m. and s.c. routes were best fitted using one-compartment open model. The collected data were subjected to a computerized kinetic analysis. The mean i.v., i.m. and s.c. elimination half-lives (t _1/2β) were 5.56 ± 0.33 h, 6.12 ± 0.42 h and 7.26 ± 0.6 h, respectively. The steady-state volume of distribution (V _dss) was 1.12 ± 0.09 L/kg and total body clearance (Cl_B) was 2.19 ± 0.1 ml/(min. kg). The absorption half lives (t _1/2ab) were 0.38 ± 0.027 h and 2.1 ± 0.09 h, with systemic bioavailabilities (F) of 96.5% ± 6.4% and 84% ± 5.5% after i.m. and s.c. administration, respectively. After i.m. and s.c. dosing, peak plasma concentrations (C _max) of 3.38 ± 0.13 μg/ml and 2.18 ± 0.12 μg/ml were attained after (t _max) 1.22 ± 0.20 h and 3.7 ± 0.52 h. The MIC₉₀ of difloxacin for Mannheimia haemolytica was 0.29 ± 0.04 μg/ml. The AUC/MIC₉₀ and C _max/MIC₉₀ ratios for difloxacin following i.m. administration were 120 and 11.65, respectively and following s.c. administration were 97.58 and 7.51, respectively. Difloxacin was 31.7–36.8% bound to calf plasma protein. Since fluoroquinolones display concentration-dependent activities, the doses of difloxacin used in this study are likely to involve better pharmacodynamic characteristics that are associated with greater clinical efficacy following i.m. administration than following s.c. administration.     

诺氟沙星在水产动物体内的药物动力学及残留研究

概述诺氟沙星在水产动物体内的药物动力学及残留研究现状,阐明诺氟沙星的药代学参数、残留规律、其影响因素以及我国氟喹诺酮类药物的应用前景。     

兽用抗寄生虫药莫奈太尔的研究进展

概述了一种新型氨基乙腈衍生物类驱虫药莫奈太尔的理化性质、作用机制、药代动力学、药效学等特点,以期为该药在兽医临床应用提供参考。     

舒巴坦匹酯在肉鸡体内药物动力学研究

本试验主要研究舒巴坦匹酯在肉鸡体内的药物动力学特征和生物利用度,为兽医临床用药提供依据。将20羽成年三黄肉鸡随机分成两组,采用单一两期交叉试验设计分别舒巴坦钠静注、舒巴坦匹酯口灌给药,利用高效液相色谱法测定血浆中药物浓度。静脉注射舒巴坦钠(舒巴坦3.75 mg/kg.B.W)后,主要药物动力学参数：t1/2α为0.090 ± 0.001 h,t1/2β为0.919 ± 0.011 h,AUC为6.137 ± 0.376 μg.h/mL,CLb为0.611 ± 0.051 L/h/kg。舒巴坦匹酯口灌给药后(舒巴坦3.75 mg/kg.B.W),舒巴坦匹酯主要药动学参数：t1/2ka为0.087 ± 0.007h,t1/2β为2.044 ± 0.165h,AUC为4.109 ± 0.364μg.h/mL,Tmax为0.412 ± 0.039h,Cmax为1.212 ± 0.092μg/mL。鸡口灌舒巴坦匹酯后,吸收迅速,分布较快,消除也较快,舒巴坦匹酯的F为66.96% ± 5.95%。     

亚硒酸钠在肉鸡体内药代动力学的研究

实验研究了30日龄肉鸡单次肌注(0.6mg/Kg)亚硒酸钠注射液后不同时间采血,用流动注射氢化物发生原子吸收光谱法测定血硒浓度,经微机处理得出血硒浓度及药动学参数,血硒浓度-时间曲线符合一级吸收一室开放模型,最佳药时方程:C=100.2001(e-0.0197t-e-1.6428t)。主要药动学参数:t1/2Ka为0.421 9h,t1/2Ke为35.121 5h,tp为3.312 4h,Cmax为93.986 5μg/L,AUC为5 025.314 9(μg/L).h。根据单剂量给药参数,计算出多剂量给药参数。     

硫酸锰在肉鸡体内药代动力学研究

实验研究了30日龄肉鸡按55.38mg/Kg.体质量剂量灌服10%硫酸锰溶液后不同时间采血,应用石墨炉原子吸收分光光度法测定血药浓度,经微机处理得出血药浓度及药动学参数,血药浓度-时间曲线符合一级吸收一室开放模型,最佳药时方程:C=80.8013(e-0.0709t-e-0.4402t)。主要药动学参数:t1/2Ka为1.5747hrs,t1/2Ke为9.7698hrs,tp为5.6617hrs,Cmax为48.3581ug/L,AUC为967.9305(μg/L).h。根据单剂量给药参数,计算出多剂量给药参数。τ定为12h,(C∝)max为95.997μg/L,c为80.6609μg/L,(C∝)min为4.0668μg/L,D*为3.2794mg/Kg.BW,D0为1.8789mg/Kg.BW,R为1.7454。