新型兽用纳米乳载药系统在大鼠体内的药代动力学研究

为了解氟苯尼考纳米乳(FFNE)在大鼠体内药代动力学行为,本试验以氟苯尼考溶液(FFSol)为参比制剂,以30 mg/kg剂量给大鼠灌胃和肌内注射给药,分别于给药后0.5、1、2、4、8、12、24、36、48、72 h采血,利用高效液相色谱法测定血浆中氟苯尼考含量,利用DAS 2.0软件计算房室模型与非房室模型条件下药代动力学参数。结果显示,在两种给药方式下,FFNE与FFSol在大鼠体内均符合二室模型。灌胃给药后,FFNE与FFSol在房室模型条件下AUC_((0-∞))分别为1 085.047和2 176.490 mg/L·h,半衰期分别为10.566和13.687 h,FFNE的相对生物利用度为187.4%。肌内注射给药后,FFNE与FFSol在房室模型条件下AUC_((0-∞))分别为1 530.55和3 243.338 mg/L·h,半衰期分别为7.533和13.335 h,FFNE的相对生物利用度为211.9%。结果表明,FFNE通过灌胃和肌内注射给药在大鼠体内分布较广,灌胃相对肌内注射吸收差,消除快。将氟苯尼考制成纳米乳剂后促进了氟苯尼考的吸收,氟苯尼考的生物利用度显著提高。     

静脉和肌内注射后氟苯尼考在麻鸭体内药动学的初步研究

试验研究了麻鸭单次静脉注射和肌内注射氟苯尼考后的药动学,给药剂量均为20 mg/kg体重。麻鸭给药后,定点采血,分离血浆,然后以高效液相色谱法测定血浆中的药物浓度,并利用房室分析法计算两种不同给药途径下氟苯尼考的药动学参数。结果显示:静脉注射氟苯尼考表观分布容积(V_β)为(8 388.45±850.43)m L/kg,消除较缓慢,消除半衰期(t_(1/2β))为(6.61±0.83)h;肌内注射氟苯尼考峰浓度(C_(max))为(1.42±0.16)μg/m L,达峰时间(t_(max))为(1.60±0.19)h,绝对生物利用度为71.59%。结果证实氟苯尼考在麻鸭体内具有优异的药动学特征,分布迅速、广泛、消除较缓慢,肌内注射吸收迅速且较完全。结合氟苯尼考对鸭疫里默氏杆菌、沙门菌及大肠杆菌的MIC数据,计算得出对如上3种细菌感染的治疗,静脉或肌内注射20 mg/kg氟苯尼考较难达到良好的治疗效果,应适当增加给药剂量。     

环糊精包合氟苯尼考在猪体内的药代动力学研究

为评价采用新包被工艺生产的氟苯尼考（受试制剂F）与国外同类产品（R1）、国内同类产品（R2）在猪体内的生物等效性并探索其药代动力学特性,本试验采用随机三制剂、三周期自身交叉试验设计,选取6头健康的阉割小公猪（体重15 kg±2 kg）,分别灌胃给药3种制剂,给药剂量为20 mg/（kg·BW）,采用高效液相色谱法测定血浆中氟苯尼考浓度,利用Kinetica 5.0软件分析药代动力学特性,SAS统计软件进行生物等效性评价。结果显示,受试制剂在猪体内的药时曲线符合带时滞的一级吸收一室开放模型,F、R1、R2的峰浓度（C_max）分别为16.0845、18.3287和21.1678 μg/mL,药物达峰时间（T_max）分别为5.0、1.9、1.5 h;药-时曲线下面积_（0-∞）（AUC_0-∞）分别为144.7327、118.2670和123.3715 μg/mL·h;受试制剂相比于两种参比制剂的相对生物利用度分别为122.51%（R1）和117.52%（R2）。结果表明,环糊精包被氟苯尼考有更好的缓释作用,具有更好的生物安全性,药效维持时间长,生物利用度有效提高。     

单次灌胃、静脉注射和肌内注射后多西环素在麻鸭体内的药动学

对麻鸭单次静脉注射、肌内注射和灌胃多西环素后进行药动学研究,给药剂量均为20 mg/kg。麻鸭给药后定点采血,分离血浆,然后以高效液相色谱法测定血浆中的药物浓度,并利用房室分析法计算3种不同给药途径下多西环素的药动学参数。结果显示:静脉注射后,多西环素分布广泛,其表观分布容积(V_d)为(768.50±119.61)m L·kg~(-1),且消除缓慢,消除半衰期(t_(1/2β))为(16.62±0.84)h;而灌胃和肌内注射后,多西环素均迅速吸收,峰浓度(C_(max))分别为(11.32±3.46),(19.70±2.79)mg·L~(-1),达峰时间(t_(max))分别为(2.51±0.23),(1.56±0.09)h,绝对生物利用度则分别为39.44%,77.67%。本研究结果证实多西环素在麻鸭体内具有优异的药动学特征,其吸收迅速、分布广泛、消除缓慢,但同时灌胃后其生物利用度较低。因此推荐多西环素在麻鸭感染性疾病治疗中的给药方案为灌胃或肌内注服给药,剂量均为20 mg·kg~(-1)·d~(-1),连用3 d。     

氟苯尼考在哺乳猪体内药代动力学研究

目的研究氟苯尼考注射液在哺乳仔猪体内的药物代谢动力学,为临床更加合理使用该药提供理论基础。方法:选取健康哺乳仔猪6头,按15mg/kg.bw肌内注射氟苯尼考,于给药后24h内采集不同时间点血浆样品,用乙酸乙酯进行二次提取,高效液相色谱-DAD检测法测定药物浓度,得到氟苯尼考在哺乳仔猪体内的药-时数据,PKS药动学软件分析得到药动学数据。结果哺乳仔猪肌内注射氟苯尼考后药动学数据符合开放式一级吸收二室模型,其重要药动学数据如下:分布半衰期tl/2α=62.12min,消除半衰期t1/2β=284.84min,药时曲线下面积AUC=75837μg·mL-·1h,tmax=100.00min,Cmax=118.96mg/L。     

泰地罗新注射液在猪体内的药代动力学及绝对生物利用度研究

为了研究泰地罗新注射液肌内注射和静脉注射在猪体内的药动学特征和绝对生物利用度,16只健康猪采用随机单剂量、平行试验设计,分别以4 mg/kg BW肌内注射和以1 mg/kg BW静脉注射泰地罗新注射液。采用超高效液相色谱-串联质谱法测定猪血浆中泰地罗新的浓度,以药动学分析软件WinNolin 6.4非房室模型计算药动学参数。结果显示,猪肌内注射泰地罗新注射液的药动学参数分别为Tmax(0.58±0.36)h,Cmax(0.88±0.17)μg/ml,AUClast(11.00±4.05)μg.h/mL,T1/2λz(33.58±22.01) h,MRTlast(35.60±10.00 )h。猪静脉注射泰地罗新注射液的药动学参数分别为AUClast(3.56±1.62)μg.h/mL,T1/2λz(50.91±23.47)h,MRTlast(37.53±4.52 )h,Vz(17.59±8.09)L/kg,Cl(0.31±0.14)L/h.kg。肌内注射泰地罗新注射液的绝对生物利用度77.15%,在猪体内的药动学特征是吸收迅速,血浆达峰时间短,消除半衰期长,绝对生物利用度高。     

呼替奇在鸡体内的药动学研究

本文进行了呼替奇在鸡体内的药动学和生物利用度研究.24只健康鸡,随机分为2组,分别单剂量20 mg·kg-1·bw灌胃呼替奇和肌内注射替米考星注射液.在给药前后不同时间点从翅下静脉采集血样,分离血浆,用高效液相色谱法测定血浆中替米考星的浓度.结果:灌胃呼替奇与肌内注射替米考星(20 mg· kg-1·bw)后的AUC分别为(16.32±3.16)、(15.96±3.72) μg×h/ml,Cmax分别为(1.43±0.54)、(1.38±0.66)μg/ml,没有显著差异,相对生物利用度为102.26±4.72％;tmax分别为(2.08±0.85)、(1.36±0.47)h,t1/2β分别为(41.26±8.38)、(36.54±5.97)h,MRT分别为(45.70±5.08)、(38.58±6.59)h,Vd分别为(1.27±0.69)、(2.02±0.82) L/kg,差异显著.试验结果表明,单剂量口服呼替奇后,吸收较快,消除缓慢,平均驻留时间显著延长.     

黄牛肌内注射酮洛芬的药代动力学及生物利用度

旨在研究黄牛静脉注射和肌内注射酮洛芬的药代动力学及肌内注射的生物利用度。选用6头健康的犊黄牛,采用双周期随机交叉试验,静脉注射和肌内注射酮洛芬的剂量均为3mg/kg体质量,采血时间点为给药前和给药后5,10,15,20,30,40,50min和1,1.5,2,3,4,6,8,10,12,14,24,30,36,48h。乙腈提取血浆中的酮洛芬,用高效液相色谱串联质谱法(HPLC-MS-MS)测定血浆中的药物浓度。使用WinNonlin 6.2药代动力学软件对静脉注射和肌内注射的血药浓度-时间数据进行分析,均采用非房室模型拟合。静脉注射给药的主要药代动力学参数为:t1/2β(4.18±0.41)h,MRT(3.40±0.52)h,Vd(387.52±46.49)kg/mL,ClB(65.29±14.40)mL·(h·kg)-1,AUC0-∞(47.70±9.41)h·mg·L-1。肌内注射给药的主要药代动力学参数为:tmax(0.50±0.10)h,Cmax(11.24±1.41)mg/L,t1/2β(4.38±0.66)h,MRT(3.83±0.34)h,AUC0-∞(42.46±3.84)h·mg·L-1,F为(91.2±11.7)%。结果表明,犊黄牛肌内注射酮洛芬后吸收迅速,血浆中峰浓度高,消除较快,生物利用度高。     

猪半体内氟苯尼考对大肠杆菌的药动学-药效学同步关系研究

采用体内药动学和体外药效学联合的方法,研究氟苯尼考在猪半体内抗大肠杆菌的活性,为合理应用氟苯尼考治疗猪大肠杆菌病提供参考.氟苯尼考在MH肉汤及血清中对猪大肠杆菌的最小抑菌浓度(MIC)分别为3.25和8.75 μg·mL-1.猪按20 mg·kg-1的剂量肌内注射氟苯尼考后,药物吸收缓慢且不规则,血浆药物达峰时间为(3.60±1.52)h,峰浓度为(5.28±1.48)μg·mL-1.氟苯尼考在猪体内消除缓慢,体内平均滞留时间为(26.61±9.81)h,消除半衰期为(17.49±8.04)h.半效浓度参数(EC50)为(7.76±4.53)h.AUC0→24h/MIC为(7.69±1.48)h,Cmax/MIC为(0.60±0.17).由于大肠杆菌对氟苯尼考的敏感性较差和氟苯尼考肌内注射药动学特征的限制,应用氟苯尼考,按照常规方案治疗猪大肠杆菌病,可能导致治疗失败.     

两种氟苯尼考注射液在鸡体内比较药动学研究

为比较两种氟苯尼考注射液的药物代谢动力学,本研究选择30只健康鸡随机分为两组,分别单剂量20 mg/kg bw肌内注射受试制剂和参比制剂,于给药后0.167、0.33、0.5、0.75、1、1.5、2、4、6、8、12、24、48 h翼下静脉采集血样。用超高效液相色谱法（UPLC-UV）测定血浆中氟苯尼考的含量,并用WinNonlin 8.1非房室模型计算主要药代动力学参数。结果显示,受试制剂和参比制剂的t1/2分别为（3.39±2.65）和（4.47±3.14）h,Tmax分别为（0.66±0.30）和（0.77±0.30）h,Cmax分别为（7.06±2.35）和（8.24±4.54）μg/mL,AUC0→t分别为（19.05±5.79）和（21.76±6.71）（μg/mL）h,AUC0→∞分别为（20.11±6.36）和（23.04±6.91）（μg/mL）h,MRT分别为（3.25±1.25）和（3.55±0.96）h,相对生物利用度为87.55%。结果表明,虽然二者主要药动学参数无显著性差异（p＞0.05）,但受试制剂相对生物利用度较低。     

Florfenicol pharmacokinetics in lactating cows after intravenous, intramuscular and intramammary administration

Pharmacokinetics of florfenicol 30% injectable solution was determined in lactating cows after intravenous, intramammary and intramuscular administration. Serum concentration-time data generated in the present study were analysed by non-compartmental methods based on statistical moment theory. Florfenicol half-life was 176 min, mean residence time 129 min, volume of distribution at steady-state 0.35 L/kg, and total body clearance 2.7 mL/min·kg after intravenous administration at 20 mg/kg. The absorption after intramuscular administration appeared slow and the kinetic parameters and the serum concentration vs. time curve were characteristic of absorption rate-dependent elimination. The absorption after intramammary administration of florfenicol at 20 mg/kg was good (53.9%) and resulted in serum concentrations with apparent clinical significance. The intramammary administration resulted in serum florfenicol concentrations that were significantly higher than the respective serum concentrations following Intravenous administration 4 h after administration and thereafter. Florfenicol absorption was faster from the mammary gland than from the muscle. The maximum serum concentrations ( C _max) were 6.9 μg/mL at 360 min after intramammary administration and 2.3 μg/mL at 180 min after intramuscular administration. The bioavailability of florfenicol was 54% and 38% after intramammary and intramuscular administration, respectively. The C _max in milk was 5.4 μg/mL at 180 min after intravenous and 1.6 μg/mL at 600 min after intramuscular administration.     

Single intravenous and oral dose pharmacokinetics of florfenicol in the channel catfish (Ictalurus punctatus)

Plasma distribution and elimination of florfenicol in channel catfish were investigated after a single dose (10 mg/kg) of intravenous (i.v.) or oral administration in freshwater at a mean water temperature of 25.4 °C. Florfenicol concentrations in plasma were analyzed by means of liquid chromatography with MS/MS detection. After i.v. florfenicol injection, the terminal half-life (t(1/2)), volume of distribution at steady state (V(ss)), and central volume of distribution (V(c)) were 8.25 h, 0.9 and 0.381 L/kg, respectively. After oral administration of florfenicol, the terminal t(1/2), C(max), T(max), and oral bioavailability (F) were 9.11 h, 7.6 μg/mL, 9.2 h, and 1.09, respectively. There was a lag absorption time of 1.67 h in oral dosing. Results from these studies support that 10 mg florfenicol/kg body weight in channel catfish is an efficacious dosage following oral administration.     

Tissue concentrations and pharmacokinetics of florfenicol in male veal calves given repeated doses

The pharmacokinetic disposition of florfenicol was studied in male veal calves given 11 mg of florfenicol/kg of body weight, IV and 11 mg of florfenicol/kg PO every 12 hours for 7 doses. After florfenicol administration IV, the median elimination half-life was 222.8 minutes, whereas the median half-life of the distribution phase was 7.94 minutes. Median body clearance and apparent volume of distribution were 2.87 ml/kg/min and 0.907 L/kg, respectively. After florfenicol administration, PO, there was a wide variation in the calculated half-life, which was attributed to variation in the rate of florfenicol absorption. The half-life was 167.4 to 534.9 minutes after the first oral dose and 190 to 808.8 minutes after the seventh dose. The median bioavailability after the first oral dose was 0.8888. Peak and trough concentrations of florfenicol were increased after subsequent doses were administered, compared with those after the first oral dose. The percentage of protein binding in serum from one adult cow was 22% to 26%. Florfenicol concentrations in tissues and body fluids of male veal calves were studied after the seventh dose of 11 mg of florfenicol/kg. High concentrations of florfenicol were measured in the urine, kidney, and bile. Low concentrations were measured in the brain, CSF, and aqueous humor. Concentrations in all other tissues and fluids studied were similar to the concurrent serum concentration.     

Bioavailability and pharmacokinetics of ibuprofen in the broiler chicken

The intravenous, intramuscular and oral pharmacokinetics of ibuprofen in broiler chickens were investigated. In a preliminary study, plasma ibuprofen concentration-time profiles, following i.v. (25 mg/kg) dosing were best described by a 2-compartment model. After intravenous administration, the volume of distribution at steady-state ( V _d(ss)), the total systemic clearance ( Cl _B), the elimination half-life (t_1/2p) and the MRT were 0.303 L/kg, 482.3 ml/h-kg, 2.71 h and 1.02 h, respectively. After intramuscular administration of ibuprofen, the t _max and C _max were 0.37 h, and 42.2μg/mL, respectively, with an estimated bioavailability of 46.7%. After oral administration of ibuprofen, the t _max and C _max were 0.31 h and 23.91 μg/mL, respectively, with an estimated bioavailability of 24.2%. This is a preliminary study, examining the use of ibuprofen in broiler chickens, and should be followed by tissue residue and efficacy studies in different disease states.     

氟苯尼考纳米晶在鸡体内的药动学

氟苯尼考(florfenicol,FFC)是新型动物广谱抗菌剂,抗菌效果好,广泛应用于牛、羊、猪、水产及禽类等动物细菌性疾病的防制.本试验旨在研究FFC和氟苯尼考纳米晶(florfenicol nanocrystal,FFC-NC)在鸡体内的生物利用度.采用交叉试验法,鸡用药后,在不同时间点翅下静脉采血,利用高效液相色...     

Tissue concentrations and pharmacokinetics of florfenicol in broiler chickens

1. Florfenicol (30 mg/kg body weight) was administered to broiler chickens via intravenous (iv), intramuscular (im) and oral routes to study its plasma concentrations, kinetic behaviour, systemic bioavailability and tissue content.

2. Following a single iv injection, the kinetic disposition of florfenicol followed a 2‐compartmental open model with an elimination half‐life of 173 min, total body clearance of 26.9 ml/kg/min and a steady state volume of distribution of 5.11 1/kg.

3. The highest plasma concentrations of florfenicol were 3.82 and 3.20 μg/ml following single im and oral administration, respectively. The systemic bioavailability was 96.6% and 55.3% after im and oral administration. The plasma protein binding of florfenicol was 18.5%.

4. Following its administration, the highest tissue concentrations of the drug were found in the kidney bile, lung, muscle, intestine, heart, liver, spleen and plasma. Low concentrations of the drug were found in brain, bone marrow and fat. No florfenicol residues were detected in tissues and plasma after 72 h except in the bile from where it disappeared after 96 h.     

Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in the Korean catfish (Silurus asotus)

The pharmacokinetics of florfenicol and its metabolite, florfenicol amine, was investigated after its intravenous (i.v.) and oral (p.o.) administration of 20 mg/kg of body weight in Korean catfish (Silurus asotus). After i.v. florfenicol injection (as a bolus), the terminal half-life (t(1/2)), the volume of distribution at steady state (V(dss)), and total body clearance were 11.12 +/- 1.06 h, 1.09 +/- 0.09 L/kg and 0.07 +/- 0.01 L x kg/h respectively. After p.o. administration of florfenicol, the t(1/2), C(max), t(max) and oral bioavailability (F) were 15.69 +/- 2.59 h, 9.59 +/- 0.36 microg/mL, 8 h and 92.61 +/- 10.1% respectively. Florfenicol amine, an active metabolite of florfenicol, was detected in all fish. After i.v. and p.o. administration of florfenicol, the observed C(max) values of florfenicol amine (3.91 +/- 0.69 and 3.57 +/- 0.65 mg/L) were reached at 0.5 and 7.33 +/- 1.15 h. The mean metabolic rate of florfenicol amine after i.v. and p.o. administration was 0.4 and 0.5 respectively.     

Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in dogs

A study on the bioavailability and pharmacokinetics of florfenicol was conducted in six healthy dogs following a single intravenous (i.v.) or oral (p.o.) dose of 20 mg kg(-1) body weight (b.w.). Florfenicol concentrations in serum were determined by a high-performance liquid chromatography/mass spectrometry. Plasma concentration-time data after p.o. or i.v. administration were analyzed by a non-compartmental analysis. Following i.v. injection, the total body clearance was 1.03 (0.49) L kg(-1)h(-1) and the volume of distribution at steady-state was 1.45 (0.82) L kg(-1). Florfenicol was rapidly distributed and eliminated following i.v. injection with 1.11 (0.94)h of the elimination half-life. After oral administration, the calculated mean C(max) values (6.18 microg ml(-1)) were reached at 0.94 h in dogs. The elimination half-life of florfenicol was 1.24 (0.64) h and the absolute bioavailability (F) was achieved 95.43 (11.60)% after oral administration of florfenicol. Florfenicol amine, the major metabolite of florfenicol, was detected in all dogs after i.v. and p.o. administrations.     

Bioavailability and pharmacokinetics of florfenicol in broiler chickens

The bioavailability and pharmacokinetic disposition of florfenicol in broiler chickens were investigated after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 15 and 30 mg/kg body weight (b.w.). Plasma concentrations of florfenicol were determined by a high performance liquid chromatographic method in which plasma samples were spiked with chloramphenicol as internal standard. Plasma concentration-time data after i.v. administration were best described by a two-compartment open model. The elimination half-lives were 168 +/- 43 and 181 +/- 71 min, total body clearance 1.02 +/- 0.17 and 1.02 +/- 0.16 L x kg/h, the volume of distribution at steady-state 4.99 +/- 1.11 and 3.50 +/- 1.01 L/kg after i.v. injections of 15 and 30 mg/kg b.w., respectively. Plasma concentration-time data after i.m. and oral administrations were adequately described by a one-compartment model. The i.m. bioavailability and the oral bioavailability of florfenicol were 95, 98 and 96, 94%, respectively, indicating that florfenicol was almost absorbed completely after i.m. and oral administrations of 15 and 30 mg/kg b.w.     

Pharmacokinetics of florfenicol and its major metabolite, florfenicol amine, in rabbits

The pharmacokinetics of florfenicol and its active metabolite florfenicol amine were investigated in rabbits after a single intravenous (i.v.) and oral (p.o.) administration of florfenicol at 20 mg/kg bodyweight. The plasma concentrations of florfenicol and florfenicol amine were determined simultaneously by an LC/MS method. After i.v. injection, the terminal half-life (t(1/2lambdaz)), steady-state volume of distribution, total body clearance and mean residence time of florfenicol were 0.90 +/- 0.20 h, 0.94 +/- 0.19 L/kg, 0.63 +/- 0.06 L/h/kg and 1.50 +/- 0.34 h respectively. The peak concentrations (C(max)) of florfenicol (7.96 +/- 2.75 microg/mL) after p.o. administration were observed at 0.90 +/- 0.38 h. The t(1/2lambdaz) and p.o. bioavailability of florfenicol were 1.42 +/- 0.56 h and 76.23 +/- 12.02% respectively. Florfenicol amine was detected in all rabbits after i.v. and p.o. administration. After i.v. and p.o. administration of florfenicol, the observed Cmax values of florfenicol amine (5.06 +/- 1.79 and 3.38 +/- 0.97 microg/mL) were reached at 0.88 +/- 0.78 and 2.10 +/- 1.08 h respectively. Florfenicol amine was eliminated with an elimination half-life of 1.84 +/- 0.17 and 2.35 +/- 0.94 h after i.v. and p.o. administration respectively.