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。     

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.     

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。     

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。     

氟苯尼考混悬剂与常规制剂在猪体内药动学的比较研究

长效制剂能够使药物在动物体内缓慢释放,使有效药物浓度维持较长时间,实现方便给药的目的,同时也克服常规制剂多次给药造成的波峰波谷现象,更好地发挥药效。氟苯尼考混悬剂和常规制剂按20mg/kg体重肌注给药,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距原理处理。氟苯尼考混悬剂的主要药动学参数:AUC=44.99μg/(mL.h),MRT=26.62h,t1/2β=16.5h;氟苯尼考常规制剂的主要药动学参数:AUC=54.3μg/(mL.h),MRT=12.97h,t1/2β=11h。试验结果表明氟苯尼考混悬剂在体内吸收缓慢,能够延长药物在体内作用时间。     

基于生理药动学模型预测肉鸡连续肌内注射氟苯尼考后各组织中的药物浓度

为了预测肉鸡连续肌内注射氟苯尼考后各组织中药物的残留浓度,利用文献检索获得的肉鸡生理学和解剖学参数及氟苯尼考在各组织中的组织-血浆分配系数,建立了一个包含13个模块的血流限速型生理药动学模型。模型中包含了氟苯尼考自注射部位的吸收、从肾脏的排泄、在肝脏的代谢及肝肠循环模块。研究利用该模型成功预测了肉鸡连续5次肌内注射氟苯尼考(30 mg/kg·d)后各组织中氟苯尼考的残留浓度。结果表明:多次肌内注射后,氟苯尼考在肉鸡体内吸收迅速、分布广泛、消除缓慢,且在注射部位浓度最高,消除最慢。     

家兔大椎穴注射扑热息痛的药动学研究

目的:研究扑热息痛注射液于家兔大椎穴注射后的药动学特征。方法:健康家兔8只,扑热息痛单剂量(20mg/kg)于大椎穴注射后,在规定时间点采血,HPLC检测血药浓度,DAS药动学软件处理药时数据。结果:药时数据符合一级吸收二室模型(权重=1/C2),主要药动学参数为:Cmax=23.1880±2.4785(mg/l),tpeak=0.5000±0.0000(h),t1/2Ka=0.3821±0.1086(h),t1/2α=2.1260±0.9838(h),t1/2β=10.1621±4.0967,AUC(0-12h)=34.5331±4.181(mg/l.h),Ka=3.7364±1.2723(h),MRT(0-12h)=1.3159±0.0581(h)。结论:扑热息痛于家兔大椎穴注射后,药物迅速达到峰值,血药浓度高,有效血药浓度维持时间长,药物体内分布广泛。     

环丙-林可霉素复方长效注射剂在猪体内的药物动力学研究

18头健康猪随机分成3组,分别按每公斤体重10 mg单剂量颈部注射环丙沙星注射液、盐酸林可霉素注射液及环丙-林可霉素长效注射液后,用高效液相色谱法分别测定环丙沙星和林可霉素的血药浓度,评价环丙-林可霉素长效注射液在猪体内的药物动力学特征。环丙-林可霉素长效注射液中环丙沙星及参比注射液主要药动学参数分别为:药时曲线下面积(AUC)23.62和15.67μg·h/mL,消除半衰期(t1/2β)12.34和5.22 h,达峰时间(Tp)1.54和0.94 h,吸收半衰期(t1/2α)0.45和0.27 h。林可霉素及参比注射液主要药动学参数分别为:AUC为25.68和18.40μg·h/mL,t1/2β为10.74和3.59 h,Tp为1.03和0.69 h,t1/2α为0.37和0.25 h。结果表明:肌内注射环丙-林可霉素长效注射液后,两药均迅速吸收,体内释放平稳,消除缓慢,具有长效和缓释的作用。     

肌内注射后氟苯尼考在肉鸡体内生理药动学模型血流图模拟设计

根据氟苯尼考在肉鸡体内的药动学特征及肉鸡的生理学、解剖学特点,设计了一个包含氟苯尼考及氟苯尼考胺两部分在内的生理药动学模型血流图。模拟肌内注射给药后药物的吸收、分布、肝脏代谢及肝肠循环等过程。为氟苯尼考及氟苯尼考胺在肉鸡体内PBPK模型的最终建立提供了思考路径。     

氟苯尼考在鸡体内的药动学及其体内抗菌后效应研究

为探讨氟苯尼考的药动学特征及抗菌后效应(PAE),制订临床给药方案,用微生物法测定鸡血清中氟苯尼考浓度。建立鸡组织笼感染模型,以菌落计数法测定氟苯尼考的体内PAE。结果显示内服给药后药-时数据符合一级吸收一室开放式模型,其药动学方程为C=4.7804(e-0.1096t-e-2.5858t),主要药动学参数:t1/2Ke=(6.42±0.83)h、Cmax=(3.96±0.42)μg/mL、AUC=(42.41±7.50)(μg/mL).h-1、Vd=(6.63±0.68)L/kg;氟苯尼考浓度在2MIC、4MIC和8MIC时,作用1h的体内PAE分别为0.35、1.20和1.48h,同时测定的体外PAE为0.23、0.93和1.17h。鸡内服氟苯尼考的给药方案为1日1次,维持剂量30mg/kg体重。     

高效液相色谱法测定猪血浆中氟苯尼考的含量

建立了猪血浆中氟苯尼考含量测定的高效液相色谱法(HPLC)。采用C18色谱柱(4.6mm×250mm,5μm),以乙腈-水(24:76)为流动相,流速1.0mL/min,检测波长223nm,进样量20μL,柱温为25℃。氟苯尼考浓度在0.1～16μg/mL时,标准曲线线性关系良好(r0.9998),无杂质干扰,回收率高于94%,批内变异系数和批间变异系数均低于5%。本方法操作简便,分析快速,结果准确,适用于猪血浆中氟苯尼考含量的测定及相关药代动力学研究。     

Pharmacokinetics of florfenicol after a single intramuscular dose in white-spotted bamboo sharks (Chiloscyllium plagiosum).

This study evaluated the pharmacokinetics of florfenicol in the white-spotted bamboo shark (Chiloscyllium plagiosum). In addition to the pharmacokinetics, the potential application for treatment of bacterial meningitis was explored. A pilot study was used to compare doses of 30, 40, and 50 mg/kg i.m. Following that study, 10 adult sharks were administered a single i.m. dose of florfenicol at 40 mg/kg. Plasma and cerebrospinal fluid were collected and analyzed for florfenicol by a sensitive and specific high-pressure liquid chromatographic method. Pharmacokinetic analysis was performed using both non-compartmental and compartmental techniques. The absorption produced an average peak at 54 (+/-19) hr from the i.m. site of administration, and the half-life was prolonged, averaging 269.79 hr (+/-135.87). Florfenicol plasma concentrations peaked at an average of 11.85 microg/ml (+/-1.45) and were maintained above our target minimum inhibitory concentration of 4-8 microg/ml for at least 120 hr. Cerebrospinal fluid concentrations peaked at an estimated 9 microg/ml around 48 hr, surpassing the target minimum inhibitory concentration for at least 72 hr.     

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.     

Bioavailability of levamisole administered by subcutaneous and oral routes in rabbits

The bioavailability of levamisole in rabbits was determined after subcutaneous and oral administration at three dose levels of 12.5, 16.0 and 20.0 mg/kg. After non-compartmental analysis the mean values obtained were: C _max=3.54, 4.51 and 5.39 μg/ml; t _max= 12.0, 22.0 and 20.0 min; F = 134.8, 105.4 and 124.1% after subcutaneous administration for each dose, respectively, and C _max= 0.71, 1.32 and 1.77 μg/ml; t _max= 46.0, 96.0 and 84.0 min; F = 53.0, 62.0 and 80.7% after oral administration. The extent and rate of absorption from the two routes differed significantly, except for t _max at the 12.5 mg/kg dose. After compartmental analysis the pharmacokinetics of levamisole was characteristic of a two-compartment open model in 13 rabbits and of a one-compartment open model in two rabbits after subcutaneous administration, while it was two compartmental in nine and one compartmental in six rabbits after oral administration. The k_a values were 0.321, 0.145 and 0.145 min^-1 after subcutaneous administration and 0.054, 0.023 and 0.027 min¹ after oral administration. There were no significant differences between the values of C _max, t _max and AUC calculated by compartmental and non-compartmental analysis.     

氟苯尼考磺酸盐在肉鸡体内的药物动力学初步研究

研究氟苯尼考磺酸盐在肉鸡体内的血药浓度及药动学特征。将12只健康三黄肉鸡,单次肌肉注射推荐治疗剂量（20mg／kg）的自制2％氟苯尼考磺酸盐。采用高效液相色谱法测定血浆药物浓度,所得数据用3P97药动软件进行分析后发现,血药浓度和时间关系符合一级吸收一室模型,选择的权重为1／C。主要药动学参数为T1／2kα：（0．28±0．04）h,T1/2Ke：（2．06±0．06）h,Cmax：（4．17±0．12）μg／mL,Tmax：（0．92±0．09）h,AUC：（16．89±0,35）μg／mL,V／F（c）：（3．52±0．13）L／kg,CL／F（s）：（1．19±0．03）L／（kg·h）,Ke：（0．34±0．01）／h,kα：（2．57±0．37）／h,A：（6．56±0．38）μg／mL。结果提示,氟苯尼考磺酸盐在肉鸡体内具有吸收迅速,分布广泛、峰浓度较高以及消除较快的动力学特征。     

Population pharmacokinetics of cefquinome in pigs

This study was performed in 145 pigs to develop a population pharmacokinetics (PPK) model by i.m. administration of cefquinome (CEQ) at the dose of 2 mg/kg in the neck muscle. Serum physiological and biochemical parameters for each pig were determined before administration. After administration, 2–4 samples were collected at random, with the sampling point evenly distributed in the three periods (<1 h, 1–4 h and >4 h). The plasma concentration of CEQ was determined by high performance liquid chromatography with UV detector. The pharmacostatistical analyses of concentration‐time data, weight, age, gender, serum physiological and biochemical parameters were performed with nonlinear mixed effect modeling (NONMEM). A one‐compartmental model with first‐order absorption and elimination adequately described the data from the study group. The optimal random effect model of pharmacokinetics parameters was of log‐normal distribution and the residual errors assumed a mixed‐type model (proportional and additive) to best explain intra‐individual variability. Covariate analysis showed that body weight is positively correlated with apparent volume of distribution (V/F) and body clearance (CL/F). The typical PPK parameters of K_a, CL, and V were 0.564/h, 5.15 L/h, and 1.36 L, respectively.     

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 levamisole in broiler breeder chickens

The pharmacokinetics of levamisole was studied in 20 broiler breeder chickens (chickens that give eggs to breed broilers). A single dose of levamisole (40 mg/kg) was administered orally or intravenously to chickens before the onset of egg production, prelay (age = 22 weeks), and repeated at the peak of egg production (age = 32 weeks). A high-pressure liquid chromatographic with ultraviolet detection method (HPLC-UV) was used for quantification of levamisole in plasma. Using compartmental analysis, levamisole followed a three-compartmental open model with mean values of alpha = 0.1224 and 0.4968, beta = 0.01663 and 0.01813, gamma = 0.002 and 0.002/min at the prelay and at the peak of egg production periods, respectively. The mean values for volume of distribution at steady state (V(ss)), determined by compartmental analysis, were significantly different for prelay and peak of egg production (8.358 and 13.581 mL/kg), respectively.     

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.