Pharmacokinetics of Clorsulon in Sheep Following Intravenous and Subcutaneous Administration

The study established a method to analyze clorsulon concentration in sheep plasma by reverse phase-high performance liquid chromatography(RP-HPLC)with an internal-standard.In plasma,clorsulon concentration within 0.01-1.0μgmL-1 and 1.0-20μgmL-1 ranges had a good linear relationship(R= 0.9991,0.9958). The average recovery of the method was 98.11±3.52%. The relative standard deviation(RSD)s% of within-day and between-day assays were less than 7 and 8% respectively. After giving clorsulon to sheep by intravenous(i.v.)or subcutaneous(s.c.)routes at a single dose of 4mgkg-1,drug concentration-time data in plasma were both fitted to a two-compartment open model. The main pharmacokinetic parameters were: 1)i.v. administration: T1/2β = 10.04 ± 0.819 h,area under the concentration versus time curve(AUC)=81.85±14.24mghL-1; 2)s.c. administration: T1/2ka= 1.36± 0.75 h,T1/2β=17.92 ± 9.19 h,Tmax=3.18±1.05h,Cmax=5.12±0.99μgmL-1,AUC=56.73±5.25mghL-1,F=71.03 ± 14.15%. The results indicated that clorsulon in sheep following a single s.c.administration was absorbed rapidly and eliminated slower than that following a single i.v.administration,and showed a better bioavailability.     

Pharmacokinetics of Quinocetone and Its Major Metabolites in Swine After Intravenous and Oral Administration

The pharmacokinetics of quinocetone and its major metabolites in healthy swine was investigated in this paper.Quinocetone was administered to 8 healthy cross-bread swine intravenously and orally at a dosage of 4 and 40 mg kg-1 body weight respectively in a randomized crossover design test with two-week washout period.A sensitive highperformance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of quinocetone and its metabolite 1-desoxyquinocetone in plasma.Plasma concentration versus time profiles of quinocetone and its metabolite l-desoxyquinocetone were analyzed by non-compartmental analysis using Winnonlin 5.2 software.Mean maximum concentrations (Cmax) for quinocetone was found to be (0.56±0.13) μg mL-1 at 2.92 h,after oral administration of quinocetone.Mean maximum concentrations (Cmax) for l-desoxyquinocetone after intravenous or oral administration of quinocetone were (0.0095±0.0012) μg mL-1 at 0.083 h and (0.0067±0.0053) μg mL-1 at 3.08 h.The apparent elimination half-lives (T1/2) for quinocetone and its metabolite 1-desoxyquinocetone were (2.24±0.24) and (5.23±0.56) h after intravenous administration of quinocetone and (2.91±0.29) and (11.85±2.89) h after oral administration of quinocetone,respectively.Mean areas under the plasma concentration-time curve (AUC0-∞) for quinocetone and 1-desoxyquinocetone were (2.02±0.15) and (0.2±0.002) μg h mL-1 respectively after intravenous administration of quinocetone,and (3.5±0.79) and (0.053±0.03) μg h mL-1 after oral administration of quinocetone,respectively.Quinocetone was rapidly absorbed and metabolized in swine after oral and intravenous administration.The plasma concentration-time curve (AUC0-∞) of 1-desoxyquinocetone were much smaller than those of quinocetone,while the elimination half-lives (T1/2) were much longer than those of quinocetone after intravenously (i.v.) or oral administration.     

Pharmacokinetics of Cyadox and Its Major Metabolites in Swine After Intravenous and Oral Administration

Pharmacokinetics of cyadox (CYX) and its major metabolites in healthy swine was investigated in this paper. 1,4- Bisdesoxycyadox (BDCYX), cyadox-1-monoxide (CYX-1-O) and quinoxaline-2-carboxylic acid (QCA), three main metabolites of cyadox, were synthesized by College of Science, China Agricultural University. Cyadox (CYX) was administered to 8 healthy cross-bread swine intravenously (i.v.) and orally (p.o.) at a dosage of 1 mg kg-1 body weight and 40 mg kg-1 body weight respectively in a randomized crossover design test with 2-wk washout period. A sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the determination of cyadox and its major metabolites in plasma. CYX and its major metabolites BDCYX, and CYX-1-O can be detected after intravenous administration of cyadox while CYX and its metabolites BDCYX, CYX-1-O and QCA can be detected after oral administration of CYX. Plasma concentration vs. time profiles of CYX and its major metabolites were analyzed by non-compartmental pharmacokinetic method. Following i.v. administration, the areas under the plasma concentration-time curve (AUC 0-∞ ) were (0.38±0.03) μg mL-1 h (CYX), (0.018±0.002) μg mL-1 h (BDCYX) and (0.17±0.02) μg mL-1 h (CYX-1-O), respectively. The terminal elimination half-lives (t 1/2λz ) were determined to be (0.93±0.07) h (CYX), (1.45±0.04) h (BDCYX), and (0.92±0.04) h (CYX-1-O), respectively. Steady-state distribution volume (Vss) of (2.14±0.11) L kg-1 and total body clearance (CL) of (2.84±0.19) L h-1 kg-1 were determined for CYX after i.v. dosing. The bioavailability (F) of CYX was 2.85% for oral administration. After single i.v. administration, peak plasma concentrations (C max ) of (1.08±0.06) μg mL-1 (CYX), (0.0068± 0.0004) μg mL-1 (BDCYX) and (0.25±0.03) μg mL-1 (CYX-1-O) were observed at T max of 0.033 h (CYX), 1 h (BDCYX) and 0.033 h (CYX-1-O), respectively. The main pharmacokinetic parameters after p.o. administration were as follows: AUC 0-∞ were (0.42±0.04) μg mL-1 h (CYX), (1.38±0.14) μg mL-1 h (BDCYX), (0.59±0.02) μg mL-1 h (CYX-1-O) and (1.48±0.09) μg mL-1 h (QCA), respectively. t 1/2λz were (4.77±0.33) h (CYX), (5.77±0.56) h (BDCYX), (4.12±0.28) h (CYX-1-O), and (8.51±0.39) h (QCA), respectively. After p.o. administration, C max s of (0.033±0.002) μg mL-1 (CYX), (0.22±0.03) μg mL-1 (BDCYX), (0.089±0.005) μg mL-1 (CYX-1-O), and (0.17±0.01) μg mL-1 (QCA) were observed at T max of (7.38±0.33) h (CYX), (7.25±0.31) h (BDCYX), (7.38±0.33) h (CYX-1-O), and (7.25±0.31) h (QCA), respectively. The results showed that CYX was slowly absorbed after oral administration and most of CYX was transformed to its metabolites in swine. The area under plasma concentration-time curve (AUC 0-∞ )of metabolites were higher than that of CYX after p.o. administration, and the elimination half-lives (t 1/2λz ) of QCA were longer than those of CYX, CYX-1-O, and BDCYX after oral administration.     

Study on Pharmacokinetics of Eprinomectin in Sheep Following Intravenous and Subcutaneous Administration

A RP-HPLC method was used for the determination of eprinomectin concentration in sheepplasma following i.v. and s.c. administration at a single dose of 0. 2 mg kg-1. Eprinomectin in plasma within2.5 - 200 ng mi-1 ranges had a good linear relationship(R=0. 9968). The average recovery of the method was99.65±3.84%. The RSD% of within-day and between-day assays were less than 10 and 12%, respectively.The extract of plasma samples were loaded onto a C18 catridge. After solvent exchange, the methanol eluatewas derivatized via the addition of 1-methylimidazole and trifluoroacetic anhydride in acetonitrile. The fluo-rescent derivative was analyzed. The main pharmacokinetic parameters were as follows, for i.v. administra-tion: T1/2β =12. 66± 2. 05 h, AUC0-t = 1.02 ± 0.3 mg h L-1 , fc =0. 13+0.05; for s.c. administration:T1/2sa = 4.42 ±l. 04 h, Cmax =0. 02±0.01 μg mi-1 , Tmax = 15.36 ± 2.91 h, t1/2K=26. 22±9.04 h, AUC0-t= 1.19±0.37 mg h L-1. The results showed that eprinomectin was distributed widely and taken long time toeliminate in sheep after i. v. adminstration. When given subcutaneously, eprinomectin had better absorptionand longer residue time in sheep. Eprinomectin was eliminated much slowly after s. c. adminstration comparedwith i.v. administration.     

Pharmacokinetics of Idazoxan in Deers Following Intramuscular Administration

The aim of this experiment was to determine the pharmacokinetics of hydrochloric idazoxan in deers plasma alter intramuscular （IM） dosing. Six clinical healthy Cervus nippon Temmincks were injected with the idazoxan solution at the dose of 0.44 mg·kg-1. Eight mL blood sample was taken from a jugular vein and plasma was separated for drug determination by using liquid chromatography with tandem mass spectrometric detection. Idazoxan pharmacokinetic parameters were simulated by noncompartmental analyses. The results showed that the absorption and elimination of hydrochloric idazoxan in plasma was quick by route of administration, the half-lives of absorption （t1/2Ka） and elimination （t1/2Kc） were （0.2094 ± 0.0341） min, and （13.1842±0.2353） min, respectively, the area under the plasma drug concentration-time curve from 0 to ∞ （AUC） was （0.0700±0.0035） （mg·mL-1）. min the maximum concentration in the plasma （Cmax） was （0,0047±0.0005） mg.mL ＇, peaking at （12.4618±0.1198） rain after dosing. In conclusion, these data indicated that the kinetics of hydrochloric idazoxan were fitted to one compartment model with first order absorption, which was characterized by rapid drug action, and fast metabolism with few residue in the blood.     

左氧氟沙星在健康鸡体内的药动学研究

报道左氧氟沙星在健康鸡体内的药动学研究。36只健康鸡单剂量内服左氧氟沙星[10mg/(kg·b·w)],采用高效液相色谱法测定血药浓度,最低检测限0.001mg/L,并以3P97药动学程序进行分析,药-时数据符合一级吸收二室模型,主要动力学参数如下:T1/2Ka为(0.815±0.043)h,T1/2α为(1.267±0.029)h,T1/2β为(3.492±0.352)h,Tpeak为(1.624±0.073)h,Cmax为(1.715±0.106)mg/L,AUC为(9.470±0.690)mg/(L·h),Tcp(ther)为6.668h,C(τ=12)为(0.789±0.058)mg/L,R为1.103±0.028,D(D=10)为(11.025±0.275)mg/(kg·b·w)。结果表明:左氧氟沙星在健康鸡吸收迅速,血药浓度较高,分布广泛,消除较为缓慢。     

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.     

Pharmacokinetics of Ivermectin in Salvelinus leucomaenis Following Two Ways of Administration

[目的]研究伊维菌素在白点鲑体内的药动学。[方法]对白点鲑以0．3mg／kg的剂量分别单次口灌和腹腔注射伊维菌素,采用高效液相色谱-紫外检测法（HPLC—UV）于给药后不同时间点连续进行采样检测,通过3p97软件分析药动学参数。[结果]在2种给药方式下,伊维菌素在血浆、肌肉、肝和肾中的药时关系均符合一级吸收一室开放模型。口灌给药方式下,血浆中药动学参数为Tmax=4．503h、Cmax=0．252mg／L、t1/2ka=0．476h、t1/2ka=331．160h、AUC=121．524（mrdL）·h;腹腔注射给药方式下,血浆中药动学参数为Tmax=2．751h、Cmax=0．230mg／L、t1/2ka=0．306h、t1/2ka=153．868h、AUC=51．689（mg／L）·h。[结论]两种给药方式下伊维菌素在白点鲑体内的药动学存在差异,腹腔注射给药比口灌给药吸收快。     

吡喹酮在绒山羊体内药代动力学的研究

应用反相高效液相色谱法测试了 6只健康绒山羊以每千克体重 10 0mg剂量口服给药后吡喹酮在体内的血药浓度 ,并进行了药代动力学研究 ,应用非线性最小二乘法处理 ,实验数据参数用一室模型描述。在口服给药后 ,经过短暂的迟滞期 [Lagtime =(0 2 3987± 0 0 95 39)h],血药浓度迅速上升 ,吸收相很快完成[t1/ 2ka=(0 33899± 0 192 94)h],达峰时间tp=(1 6 45 6 8± 0 43788)h ,之后是一缓慢的消除相 [t1/ 2kel=(6 2 3789± 0 70 6 2 7)h],表观分布容积Vd=(2 3 6 8130± 13 16 197)L/kg ,机体清除率CLB =[(2 6 2 3 46±1 473 10 )mg/(kg·h) ],药时曲线下面积AUC =[(5 0 0 73 2 7± 2 6 12 482 ) μg/(mL·h) ],最高血药浓度Cmax=(4 89990± 2 830 6 4) μg/mL。对吡喹酮在绒山羊体内血药浓度实测值与理论值进行卡平方检验 ,结果表明二者之间没有显著性差异 (P >0 0 5 )。     

多拉菌素在犬体内药代动力学研究

 采用RP-HPLC法荧光监测器测定单剂量皮下注射多拉菌素［300μg/（kg BW）］）后，犬体内不同时间点的血浆药物浓度。血浆药物浓度-时间数据采用3P97药动软件分析。结果表明，本试验条件下血浆中药物添加浓度在0.1～100 ng/mL范围内与峰面积呈良好线性关系，检测限为0.5 ng/mL。不同浓度水平的日内日间变异系数分别小于3%和4%，各浓度的平均回收率均大于90%。给药后血药浓度－时间数据符合一级吸收一室开放模型，主要药物动力学参数为：t_1/2ka为（0.58±0.13）d，t_1/2β为（4.78±0.31）d，T_max为（2.00±0.29）d，C_max为（20.29±2.04）ng/mL，AUC为（187.43±24.99）（ng·d）/mL。提示多拉菌素在犬体内血药浓度维持的时间长，消除缓慢，且根据其半衰期判断，多拉菌素属于慢性消除药物。     

猪饥饿和喂饲后内服氟甲砜霉素的药动学比较

报道了猪饥饿及喂饲后 5min单剂量 (2 0mg/kg)内服氟甲砜霉素的药动学比较的研究 .用高效液相色谱法测定血药浓度 .试验所得的血浆浓度 时间数据采用非房室模型统计矩原理分析处理 .猪饥饿后内服给药的主要药物动力学参数 :AUC =(91 40± 7 5 1)mg·h/L ,MRT =(7 15± 0 5 8)h ,t1/ 2 β=(5 99± 0 2 6 )h .猪喂饲后 5min内服给药的主要药物动力学参数为 :AUC =(88 47± 2 2 1)mg·h/L ,MRT =(10 94± 1 0 6 )h ,t1/ 2 β=(6 44± 0 90 )h .试验结果表明 ,猪喂饲后内服氟甲砜霉素的生物利用度与饥饿后的相似 ,但峰浓度显著小于饥饿后的峰浓度 ,两者的消除半衰期相似 .     

氟苯尼考单剂量腹腔注射和灌服后在鲫体内的药代动力学

将健康鲫150尾随机分成两组,按30mg.kg-1剂量分别单次腹腔注射和灌服氟苯尼考,用高效液相色谱法研究其在鲫体内的药代动力学特征,数据用3p97药代动力学软件分析。结果表明,腹腔液射和灌服两种给药方式的血药经时过程均符合一级吸收一室开放模型。腹腔注射和灌服给药的动力学方程分别为ρ=3.465 5(e-0.51t-e-14.88t)和ρ=7.669 9(e-0.04t-e-0.12t)。药时曲线下面积(AUC)分别为(3.905±0.056)和(1.803±0.133)mg.L-1.h;分布速率半衰期(t1/2Ka)分别为(0.047±0.001)和(5.962±0.021)h,消除速率半衰期(t1/2Ke)分别为(1.367±0.025)和(16.763±0.017)h,体清除率(CLB)分别为(0.102±0.001)和(0.018±0.017)L.kg-1.h-1,最高血药质量浓度(ρmax)分别为(25.289±2.664)和(42.137±3.887)mg.L-1。     

盐酸特比萘芬胶囊在比格犬体内的药物动力学及生物利用度研究

为了研究盐酸特比萘芬胶囊在比格犬体内的药物动力学(简称药动学)特征及生物利用度,选用健康比格犬8只,进行单剂量(10 mg·kg-1)静脉注射特比萘芬注射液和口服盐酸特比萘芬胶囊,采用双周期随机交叉试验设计,用反相高效液相色谱法测定血药质量浓度,利用Winnolin 5.2.1非房室模型计算各药动学参数.结果表明,静注盐酸特比萘芬主要药动学参数为:AUC0-∞=(5.47±1.03)μg·mL-1·h,Vss=(2.55±0.89)L·kg-1,CL=(1.88±0.33)L·h-1·kg-1,t1/2=(3.02±1.70)h;口服盐酸特比萘芬胶囊主要药动学参数为:tmax=(1.09±0.37)h,Cmax=(0.39±0.04)μg·mL-1,AUC0-∞=(0.67±0.18)μg·mL-1·h,Vd/F=(35.17±6.58)L·kg-1,t1/2=(1.69±0.74)h.比格犬口服盐酸特比萘芬胶囊的绝对生物利用度为(12.54±3.43)%.特比萘芬在比格犬体内吸收迅速,消除快,生物利用度低.     

2种剂型麻保沙星在健康家犬体内药物动力学比较

选用健康家犬6只,按随机交叉设计试验,单剂量给药均为每千克体重2.75 mg,用高效液相色谱法测定血药浓度,并应用3P97计算药物动力学参数。结果肌肉注射与口服麻保沙星的药时数据符合一级吸收一室开放模型,主要药物动力学参数如下:T1/2ka(吸收半衰期)分别为(0.52±0.41)h和(0.41±0.13)h,T1/2ke(消除半衰期)为(4.40±1.86)h和(6.25±1.80)h,Tpeak(峰时间)为(1.53±0.75)h和(1.68±0.39)h,Cmax(峰浓度)为(1.36±0.38)μg/mL和(0.93±0.06)μg/mL,AUC(药时曲线下面积)为(10.64±2.66)(μg.h)/mL和(8.68±1.98)(μg.h)/mL。乳酸麻保沙星在健康家犬口服与注射给药吸收迅速,表观分布容积大,消除缓慢,口服给药较肌肉注射吸收后分布的组织更深更广。     

不同给药方式下恩诺沙星在鲤体内的药动学研究

对两组鲤分别进行腹腔注射、口灌恩诺沙星后,应用高效液相色谱法测定了其组织中的药物浓度,研究了恩诺沙星在鲤（Cyprinus carpio）体内的吸收、分布与消除等药代动力学参数．结果表明：两种给药方式下,鲤血浆、肝脏、肾脏和肌肉组织的药时曲线符合一级消除二室模型．腹腔注射给药血浆动力学参数：AUC为59．1856μg·h·mL^-1、K为75．7627h^-1、t1／2B为96．5456h、T（peak）为0．0730h、C（max）为3．2970μg·mL^-1;灌服给药血浆动力学参数：AUC为600．2961μg·h·mL^-1、Ka为0．1693h～、t1／2β为168．2871h、T（peak）为3．6655h、C（max）为3．2661μg·mL^-1．这说明腹腔注射给药比口灌给药吸收快,血药达峰时间短,达峰浓度高．     

猪静注、肌注氟尼辛葡甲胺的药物动力学研究

 【目的】为了研究氟尼辛葡甲胺在健康猪体内的药动学。【方法】14头健康猪，按照随机拉丁方设计，进行单次不同给药剂量（2.2，1.1 mg•kg-1bw）静注和肌注。血浆样品经乙腈沉淀血浆蛋白，高速离心，用反相高效液相色谱法测定猪血浆中氟尼辛葡甲胺的浓度，3P97药动学计算软件处理血浆药物浓度－时间数据。【结果】健康猪静注给药的药时数据适合二室开放模型，2.2、1.1mg•kg-1bw剂量组主要药动学参数分别为：t1/2α（0.49±0.03）h，（0.58±0.07）h；t1/2β（6.28±0.13）h，（7.37±0.59）h；V/F（0.01±0.001）L•kg-1，（0.01±0.002）L•kg-1；CL（0.01±0.002）L•h-1，（0.01±0.002）L•h-1；AUC（237.73±52.46）μg•h•ml-1，（147.71±36.76）μg•h•ml-1。健康猪肌注给药的药时数据适合一级吸收二室模型，2.2 mg•kg-1bw、1.1 mg•kg-1bw剂量组主要药动学参数为：t1/2α(0.90±0.07)h，(0.86±0.10)h；t1/2β(8.79±0.85)h，(9.60±0.10)h，V/F(0.02±0.004)L•kg-1，(0.02±0.003)L•kg-1；CL(0.01±0.002)L•h-1，(0.01±0.003)L•h-1；AUC(174.63±45.84)μg•h•ml-1，(112.42±31.19)μg•h•ml-1。【结论】氟尼辛葡甲胺在健康猪体内肌注的主要药动学特征为吸收迅速，达峰时间短，生物利用度较高，半衰期较长。