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·bw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,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。     

硫酸锌在肉鸡体内药代动力学研究

实验研究了30日龄肉鸡单剂量52.86 mg/kg·BW剂量灌服1％硫酸锌溶液不同时间采血,应用火焰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:Ci=27.63626 (e-0.166907t-e-0.0.35005t).主要药动学参数:t1/2Ka为1.98014 hrs,t1/2Ke为4.15290 hrs,tp为4.52561hrs,Cmax为7.36195μg/L,AUC为86.62806(μg/L)·h.根据单剂量给药参数,计算出多剂量给药参数.     

健康仔猪口服亚硒酸钠后血液中药代动力学的研究

本实验按 0 .6 mg/ kg BW单剂量对健康仔猪口服亚硒酸钠溶液后 ,首次系统地研究了其在血液中药物代谢动力学。实验结果表明 :血液动力学特征符合一级吸收二室开放模型 ,其理论方程为 :C=0 .0 82 0 e- 0 .0 4 2 1 t 0 .10 5 0 e- 0 .0 0 1 4t- 0 .1870 e- 2 .2 541 t。主要动力学参数为 :吸收半衰期 (t1 / 2 Ka)为 0 .30 75 h;达峰时间 (tmax)为 2 .15 17h;消除半衰期 (t1 / 2β)为 5 10 .2 70 6 h;曲线下面积 (AU C)为 75 .14 6 0 mg/ L· h;表观分布容积 (Vd)为 5 .5 74 2 L/ kg。根据单剂量药动学参数 ,计算多剂量给药参数 ,为临床治疗制订给药方案。先导剂量 (D* )为 1.2 2 6 2 mg/ kg BW,维持剂量(D0 )为 0 .6 m g/ kg BW,给药间隔 (τ)为 4 80 h,平均稳态血药浓度 (с)为 0 .15 6 6 μg/ m l     

健康仔猪口服亚硒酸钠的血液中药代动力学的研究

本实验按0.6mg/kgBW单剂量对健康仔猪口服亚硒酸钠溶液后，首次系统地研究了其在血液中药物代谢动力学。实验结果表明，血液动力学特征符合一级吸收二室开放模型，其理论方程为：C＝0.0820e^-0.0421t 0.1050e^-0.0014t-0.1870e^-2.2541t。主要动力学参数为：吸收半衰期（t1/2Ka)为0.3075h，达峰时间（tmax)为2.1517h；消除半衰期（t1/2β）为510.2706h，曲线下面积（AUC）为75.1460mg/L.h；表观分布容积（Vd)为5.5742L/kg。根据单剂量药动学参数，计算多剂量给药参数，为临床治疗制订给药方案，先导剂量（D^*)为1.2262mg/kg BW，维持剂量（D0）为0.6mg/kgBW，给药间隔（τ）为480h，平均稳态血药浓度（c)为0.1566μg/ml。     

乳炎消在奶牛体内的药代动力学研究

给乳牛单剂量肌注0.73mg/kg乳炎消后不同时间采集血样，采用紫外分光光度法测定血药浓度。应用MCPKP药动学程序自动拟合处理血药浓度－时间数据，并求出药动学参娄。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Ci=17.8(e^-0.333t-e^-1.57t)。主要药动学参数：t1/2Ka为0.441h,t1/2K为2.082h,tmax为1.395h,Cmax为11.671μg/mL，AUC53．477mg/lh,Tcp为12.733h。根据单剂量给药参数计算出多剂量给药参数：г为12h,D^*为0.mL/kg,D（维持剂量）为0.08mL/kg。     

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。     

单诺沙星在蛋雏鸡体内的药物动力学及生物利用度的研究

选用 4～ 5周龄健康蛋雏鸡 12 5只 ,按 5 mg/kg的剂量进行静脉注射和内服单诺沙星的药动学研究及生物利用研究。高效液相色谱内标法测定血浆中药物浓度 ,MCPKP药动学程序处理药时数据。静脉注射和内服给药后血药浓度—时间数据分别符合无吸收因素二室开放式模型和一级吸收一室开放式模型。静脉注射给药的主要药动学参数为 :t1 /2α=0 .3313h、t1 /2β= 5 .994 0 h、Vd=7.5 2 4 6 L/kg、AU C=5 .6 916 μg/m l· h、CLB=0 .8935 L/kg· h。内服给药后主要药动学参数为 :t1 /2 Ka=0 .30 2 9h、t1 /2 K=6 .5 12 8h、tmax=1.2 10 0 h、Cmax=0 .5 15 9μg/m l、AU C=5 .132 9μg/ml· h。生物利用度为 90 .18%。     

三苯双脒肠溶片在羊体内药物代谢动力学试验

为研究三苯双脒在绵羊体内动态变化的规律,采用方法如下:绵羊1次口服给药60、120、180 mg/kg体重3个剂量组,依据消除速率常数、吸收率常数、达峰时、血药浓度-时间曲线等主要药动学参数,经上海宏能软件有限公司开发的临床药物代谢动力学软件进行数据分析,符合血管外给药一级吸收一室模型,主要药动学参数为:吸收率常数Ka=0.15129h,t1/2Ka=4.74h,消除速率常数Ke=0.082 121h,t1/2Ke=8.46h,t1/2=19.03 h,达峰时tmax=8.0 h,Cmax=6257μg/L,血药浓度-时间曲线下面积AUC=300 51μg/L.h。三苯双脒肠溶片在羊体内吸收快、半衰期长等特点。说明三苯双脒肠溶片在药效试验剂量范围内比较安全。     

单次肌注亚硒酸钠在仔猪体内的药代动力学

按 0 .2 m g/ kg单剂量对健康仔猪肌注亚硒酸钠溶液后 ,研究了其在血液中的药物代谢动力学。结果表明 :血液动力学特征符合一级吸收二室开放模型 ,其理论方程为 :C=0 .1773e- 0 .0 548t+0 .0 72 7e- 0 .0 0 2 6 t- 0 .2 5 0 0 e- 1 3.882 3t。主要动力学参数为 :吸收半衰期 (t1 /2 Ka)为 0 .0 4 99h;达峰时间 (tmax)为 0 .4 2 37h;消除半衰期 (t1 /2β)为 2 71.9311h;曲线下面积 (AU C)为 31.72 6 0 m g/ L·h;表观分布容积 (Vd)为 2 .4 72 1L/ kg。根据单剂量药动学参数 ,计算多剂量给药参数 ,为临床治疗制定给药方案。先导剂量 (D* )为 0 .5 0 89m g/ kg,维持剂量 (D0 )为 0 .2 mg/ kg,给药间隔 (τ)为 192 h,平均稳态血药浓度 (c)为 0 .16 5 2 mg/ L。     

单诺沙星在雏鸡体内的药动学及其抗菌后效应研究

本论文以高效液相色谱(HPLC)内标法为定量手段,研究了单诺沙星经静注、口服两种途径给药后在雏鸡体内的药物代谢动力学特征;以菌落计数法测定了单诺沙星对大肠杆菌、金黄色葡萄球菌(金葡球菌)的体外抗菌后效应。静注和内服给药后血药浓度-时间数据分别符合无吸收因素二室开放式模型和一级吸收一室开放式模型。静注给药的主要药动学参数为:t1/2α0.3313h、t1/2β5.9940h、Vd7.5246L/kg、AUC5.6916μg/(mL·h)、CLB0.8935/(kg·h)。内服给药后主要药动学参数为:t1/2Ka0.3029h、t1/2K6.5128h、tmax1.2100h、Cmax0.5159μg/mL、AUC5.1329μg/(mL·h),生物利用度为90.18%。抗菌后效应(PAE)结果如下,浓度分别为0.5MIC、2MIC、4.MIC的单诺沙星对大肠杆菌的PAE测定值分别为(0.6464±0.0294)h,(1.2077±0.0284)h,(1.6529±0.0496)h,对金葡球菌的PAE测定值分别为(0.5660±0.0075)h,(1.1746±0.0057)h,(1.4913±0.0257)h。     

Pharmacokinetics of thiamphenicol in Japanese quails (Coturnix japonica) after single intravenous and oral administrations

Thiamphenicol (TP) pharmacokinetics were studied in Japanese quails (Coturnix japonica) following a single intravenous (IV) and oral (PO) administration at 30 mg/kg BW. Concentrations of TP were determined with HPLC and were analyzed by a noncompartmental method. After IV injection, elimination half-life (t_1/2λz), total body clearance (Cl_tot) volume of distribution at steady state (V_dss), and mean residence time (MRT) of TP were 3.83 hr, 0.19 L/hr/kg, 0.84 L/kg, and 4.37 hr, respectively. After oral administration of TP, the peak plasma concentration (C_max) was 19.81 μg/ml and was obtained at 2.00 hr (t_max) postadministration. Elimination half-life (t_1/2λz) and mean absorption time (MAT) were 4.01 hr and 1.56 hr, respectively. The systemic bioavailability following oral administration of TP was 78.10%. TP therapy with an oral dosage of 30 mg/kg BW is suggested for a beneficial clinical effect in quails.     

Pharmacokinetics of florfenicol in crucian carp (Carassius auratus cuvieri) after a single intramuscular or oral administration

The pharmacokinetics of florfenicol (FF) was studied in plasma after a single dose (40 mg/kg) of intramuscular (i.m.) or oral gavage (p.o.) administration to crucian carp (Carassius auratus cuvieri) in freshwater at 25 °C. Ten fish per sampling point were examined after treatment. The data were fitted to two-compartment open models follow both routes of administration. The estimates of total body clearance (CL(b) ), volume of distribution (V(d) /F), and absorption half-life (T(1/2(ka)) ) were 0.067 L/h/kg and 0.145 L/h/kg, 2.21 L/kg and 1.04 L/kg, 2.75 and 1.54/h following i.m. and p.o. administration, respectively. After i.m. injection, the elimination half-life (T(1/2(β)) ) was calculated to be 38.2h, the maximum plasma concentration (C(max) ) to be 16.82 μg/mL, the time to peak plasma FF concentration (T(max) ) to be 1.50 h, and the area under the plasma concentration-time curve (AUC) to be 597.4 μg/mL·h. Following p.o. administration, the corresponding estimates were 2.17 h, 29.32 μg/mL, 1.61 h, and 276.1 μg/mL·h.     

口服亚硒酸钠在肉鸡体内药代动力学的研究

实验研究了30日龄肉鸡单次口服（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,血硒浓度一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-9·0197t—e-6428‘）。主要药动学参数：（1／2Ka为0．4219h,t1／2Ke为35．1215h,t。为3．3124h,Cmax为93．9865tLg／L,AUC为5025．3149％g／L）·h。根据单剂量给药参数,计算出多剂量给药参数。     

Pharmacokinetics of flumequine in sheep after intravenous and intramuscular administration: bioavailability and tissue residue studies

The pharmacokinetic properties of flumequine and its metabolite 7-hydroxyflumequine were determined in six healthy sheep after single intramuscular (i.m.) and intravenous (i.v) injections at a dose of 6 mg/kg body weight. The tissue residues were determined in 20 healthy sheep after repeated i.m. administration with a first dose of 12 mg/kg and nine doses of 6 mg/kg. The flumequine formulation used was Flumiquil 3% Suspension Injectable®. The mean plasma concentrations of flumequine after i.v. administration were described by a three-compartment open model with a rapid distribution and a relatively slow elimination phase. The low value of volume of distribution at steady state (V_dss) (0.52 ± 0.24 L/kg) and high value of volume of distribution (V_dλ₃) (5.05 ± 3.47 L/kg) emphasized the existence of a small compartment with a slow rate of return to the central compartment. The mean elimination half-life was 11.5 h. The 7-hydroxyflumequine plasma levels represented 2.3% of the total area under the curve. The mean plasma concentrations of flumequine after i.m. administration were characteristic of a two-compartment model with a first order absorption. The mean maximal plasma concentration (1.83 ± 1.15 μg/mL) was obtained rapidly, i.e. 1.39 ± 0.71 h after the i.m. administration. The fraction of dose absorbed from the injection site was 85.00 ± 30.13%. The minimal concentrations of flumequine during repeated treatment were significantly lower in females than in males. Eighteen hours after the last repeated i.m. admini-stration, the highest concentration of flumequine was observed at the injection sites followed by kidney, liver, muscle and fat. The highest concentration of 7-hydroxyflumequine was observed in the kidney and was ten times lower than the flumequine concentration. The longest flumequine elimination half-life was observed in the fat.     

Deconvolution study of the absorption rate and disposition kinetic values of lindane in sheep.

Absorption rate and plasma and fat disposition of lindane after various lindane percutaneous treatments in shorn and unshorn sheep were investigated. To analyze data with a deconvolution method, IV administration was performed to determine the basic pharmacokinetic values of lindane in sheep. After IV administration, the steady state volume of distribution was very high (8.07 +/- 3.60 L/kg of body weight), and the mean residence time was long (28.1 +/- 11.7 hours). Deconvolution analysis indicated that lindane absorption was continuous until 33 to 41 days after spraying with a 0.025% lindane solution. Total amount of absorbed lindane in shorn (15,171 +/- 4,463 micrograms/kg) sheep was about twice that in unshorn (7,615 +/- 3,128 micrograms/kg) sheep; from deconvolution analysis, it was calculated that the time required for 50% of the available dose to be absorbed was between 115 and 179 hours. After percutaneous lindane administration, the fat concentration was compared with the available lindane dose. The apparent half-life of lindane elimination in fat was 225 +/- 47.4 hours, which is similar to the value calculated for the absorption rate constant. By comparing fat and plasma concentrations, it was calculated that for a mean plasma concentration of 5 ng/ml, the fat lindane concentration was 1.65 +/- 0.87 micrograms/g (ie, lower than the generally accepted tolerance level of 2 micrograms/g).     

Oxytetracycline Pharmacokinetics in Rainbow Trout during and after an Orally Administered Medicated Feed Regimen

Abstract

The pharmacokinetic–pharmacodynamic predictor of antimicrobial activity for tetracyclines is reported to be the area under the concentration–time curve at steady state (AUC_ss) divided by the minimal inhibitory concentration of the targeted pathogen. Here, we estimate AUC_ss values for oxytetracycline (OTC) in serum of rainbow trout Oncorhynchus mykiss by using a destructive sampling study design. Seventy-two rainbow trout were fed OTC-medicated feed at 74.7 ± 1.5 mg/kg (mean ± SD) body weight (BW) by oral gavage for 10 consecutive days. Serum was collected from nine fish at 1, 3, 6, 8, 10, 12, 15, and 22 d after dosing began. Serum OTC concentrations were measured by high-performance liquid chromatography with a 0.01-μg/mL limit of detection. The average OTC AUC_ss was 29.2 μg × h/mL and was estimated using nonlinear mixed-effects modeling and bootstrap resampling techniques. The elimination half-life was estimated as 85.0 h, and the fraction of steady state achieved was estimated as 0.85. The calculated AUC_ss (24.8 μg × h/mL) following 10 d of oral dosing with 75 mg OTC/kg BW was less than the estimated AUC_ss. Results suggest that the pharmacokinetics of OTC exposure, including the AUC_ss, is better evaluated by using multiday dosimetry than by using a standard single-dose protocol.

Received September 29, 2011; accepted January 30, 2012     

地克珠利在雏鸡体内的药动学研究

目的应用高效液相色谱测定单次给药后雏鸡体内地克珠利的血药浓度,研究其药动学规律。方法44羽雏鸡按10mg／kg．BW经口单次灌服地克珠利预混剂,采用高效液相色谱系统的流动相为乙腈：0．1％三氟乙酸：水,流速1．0mL／min,分流比57：20：23,固定相为TC-C18柱,检测波长280nm,测定地克珠利血浆浓度,计算其药动学参数。结果在0．3125～20μg／mL范围内,地克珠利血药浓度呈线性关系,最低检测浓度为0．16μg／mL,回收率在79．75％以上,日内RSD小于5．68％。单剂量给药后地克珠利的主要药动学参数为：血药浓度峰值（Cmax）32．97μg／mL,达峰时间（Tpeak）1．64h,消除半衰期（T1／2β）24．29h,药时曲线下面积（AUC）349．47（mg／L）·h,血浆清除率（CL）0．03mg／kg·h。结论地克珠利在雏鸡体内代谢符合一级吸收的二室模型,药物吸收比较快和消除缓慢。     

Pharmacokinetics of single-dose intravenous or intramuscular administration of gentamicin in roosters

Healthy mature roosters (n = 10) were given gentamicin (5 mg/kg of body weight, IV) and, 30 days later, another dose IM. Serum concentrations of gentamicin were determined over 60 hours after each drug dosing, using a radioimmunoassay. Using nonlinear least-square regression methods, the combined data of IV and IM treatments were best fitted by a 2-compartment open model. The mean distribution phase half-life was 0.203 +/- 0.075 hours (mean +/- SD) and the terminal half-life was 3.38 +/- 0.62 hours. The volume of the central compartment was 0.0993 +/- 0.0097 L/kg, volume of distribution at steady state was 0.209 +/- 0.013 L/kg, and the total body clearance was 46.5 +/- 7.9 ml/h/kg. Intramuscular absorption was rapid, with a half-life for absorption of 0.281 +/- 0.081 hours. The extent of IM absorption was 95 +/- 18%. Maximal serum concentration of 20.68 +/- 2.10 micrograms/ml was detected at 0.62 +/- 0.18 hours after the dose. Kinetic calculations predicted that IM injection of gentamicin at a dosage of 4 mg/kg, q 12 h, and 1.5 mg/kg, q 8 h, would provide average steady-state serum concentrations of 6.82 and 3.83 micrograms/ml, with minimal steady-state serum concentrations of 1.54 and 1.50 micrograms/ml and maximal steady-state serum concentrations of 18.34 and 7.70 micrograms/ml, respectively.     

Pharmacokinetics of florfenicol in the plasma of Japanese quail

Abstract

AIM: To determine the pharmacokinetics and bioavailability of florfenicol in the plasma of healthy Japanese quail (Coturnix japonica).

METHODS: Sixty-five quail were given an I/V and I/M dose of florfenicol at 30 mg/kg bodyweight (BW). A two-period sequential design was used, with a wash-out period of 2 weeks between the different routes of administration. Concentrations of florfenicol in plasma were determined using high-performance liquid chromatography (HPLC).

RESULTS: A naíve pooled data analysis approach for the plasma concentration-time profile of florfenicol was found to fit a non-compartmental open model. After I/V administration, the mean residence time (MRT), mean volume of distribution at steady state (V_ss), and total body clearance of florfenicol were 12.0 (SD 0.37) h, 8.7 (SD 0.22) L/kg, and 1.3 (SD 0.08) L/h/kg, respectively. After I/M injection, the MRT, mean absorption time (MAT), and bioavailability were 12.3 (SD 0.37) h, 0.2 (SD 0.02) h, and 79.1 (SD 1.79)%, respectively.

CONCLUSIONS: The time for the concentration of florfenicol to fall below the probable effective concentration of 1 µg/ml of approximately 10 h is sufficient for the minimum inhibitory concentration needed for many bacterial isolates. Further pharm acodynamic studies in quail are needed to evaluate a suitable dosage regimen.