磺胺甲嗯唑在大菱鲆体内药代动力学及残留消除规律的研究

采用高效液相色谱法,对以80mg／kg b．W．单剂量口灌磺胺甲嗯唑的大菱鲆进行连续采样监测,研究大菱鲆口服磺胺甲嗯唑的药代动力学特征及残留消除规律。结果表明,磺胺甲嗯唑在大菱鲆血液、肌肉中药代动力学特征分别符合带时滞的一级吸收二室开放模型、一级吸收一室开放模型。磺胺甲嗯唑在大菱鲆体内消除速度较慢,16℃水温的实验条件下,在大菱鲆肌肉中的休药期为27天。     

喹乙醇及其主要代谢物在罗非鱼体内的药物动力学研究

采用高效液相色谱-质谱法,研究肌肉注射给药方式下,喹乙醇及其代谢物在罗非鱼(Tilapiafish)体内的药物代谢动力学.罗非鱼注射给药20 mg/kg后,其血浆、肌肉、肝脏中药物浓度-时间曲线关系符合一级吸收的二室开放动力学模型.喹乙醇在罗非鱼体内消除较快,在血液、肌肉、肝脏中的消除半衰期(t 1/2β)分别为5.2...     

亚硒酸钠在雏鸡体内的组织动力学研究

采用荧光法对亚硒酸钠在正常硒水平蛋用维鸡组织内的动力学过程进行了研究,结果表明,给雏鸡以０．６ｍｇ／ｋｇ体重口服,１．０ｇ／Ｌ亚硒酸钠后,肝,肾,胰均符合一级吸收二室开放模型,肌肉符合滞后一级吸收一室开放模型。整个试验过程中,肝,肾中硒的含量明显高于胰和肌肉,给药后２４ｈ每１ｇ器官和组织中含硒量依次为肝０．８４７６μｇ,肾０．７７２６μｇ,胰０．５９７８μｇ,肌肉０．１０５０μｇ,给药后１９２ｈ由     

盐酸苯噁唑在鹿体内的药代动力学研究

本研究的主要目的是建立鹿血浆盐酸苯嗯唑浓度反相高效液相色谱紫外检测法,探讨盐酸苯噁唑在鹿血浆中的药代动力学.6只临床健康的梅花鹿,同一环境下饲养后肌内注射盐酸苯恶唑(0.44 mg·kg-1),颈静脉采血8 mL后分离血浆,通过建立的高效液相色谱检测法,测定各采血时间的血浆药物浓度.结果表明,盐酸苯噁唑单剂量肌内注射给药后,药代动力学符合吸收一室模型,药代动力学参数吸收半衰期(t1/2Ka)、消除半衰期(t1/2Ke)分别为(2.09±0.34)、(13.18±0.24)min,血浆药时曲线下面积(AUC0→∞)为(70±3.50)(μg·mL-1)·min,最大血药浓度(Cmax)为(4.70±0.50)μg·mL-1,血药达峰时间(Tpeak)为(12.46±0.12)min.试验结果提示,盐酸苯噁唑在鹿体内吸收快,消除迅速,4 h后血浆中无药物残留.     

硫酸铜在肉鸡体内药代动力学研究

本文用原子吸收分光光度法测定了口服硫酸铜在肉鸡体内的全血铜浓度,用3p87实用药代动力学计算程序在微机上计算出了药代动力学参数,血铜浓度-时间曲线符合一级吸收一室开放模型,最佳药时方程:C=67.6756(e-0.0433t-e-0.9808t)。并根据单剂量药动力学参数,计算出多剂量给药参数。     

重组猪干扰素α1冻干粉针剂在猪体内的药代动力学研究

为研究重组猪干扰素α1 (rPoIFN-α1)冻干粉针剂在猪体内的药代动力学特征,本研究将实验猪随机分为3组:分别静脉、肌肉和皮下注射rPoIFN-α1 1.0×107 IU,每组设立对照组,于注射后间隔不同时间采血,采用细胞病变抑制法测定其血清样品中rPoIFN-α1的效价.结果表明,肌肉注射组和皮下注射组药动学特征符合一室开放模型,呈一级动力学消除,血药峰时间(Tmax)分别为2.872±0.314 h和4.000±0.539 h,消除半衰期(T1/2)分别为6.236±0.551 h和6.644±0.751 h,血药峰浓度(Cmax)分别为3.980±2.875× 104 IU/L和1.080±0.986× 104 IU/L.静脉注射组符合二室开放模型,呈一级动力学消除,分布半衰期(T1/2α)为0.136±0.021 h,消除半衰期(T1/2β)为5.195±0.351 h,Cmax值为6.380±0.546× 104 IU/L.rPoIFN-α1静脉、肌肉和皮下注射组清除率分别为0.930±0.132 L/h、0.677±0.228 L/h和0.879±0.210 L/h.与静脉注射组相比,肌肉注射组的生物利用度为47.82％,皮下注射组的生物利用度为35.09％.本实验结果提示这3种rPoIFN-α1的注射方法在猪体内吸收、消除较快,具有线性动力学特征.rPoIFN-α1肌肉注射给药的生物利用度高于皮下注射组,消除半衰期比静脉注射组延长,可以作为替代静脉注射的一种方便和安全给药途径.     

甲砜霉素在红笛鲷体内的组织分布和药代动力学研究

研究腹腔注射和口灌给药方式下甲砜霉素在红笛鲷体内的组织分布和药代动力学特征.甲砜霉素单剂量10 mg/（kg· bw）分别腹注和口灌红笛鲷,给药后取血浆、肌肉、肝脏和肾脏,各组织中药物浓度用HPLC-MS/MS测定,所得药时数据用DAS3.0软件分析.结果显示：两种给药方式下红笛鲷血浆药时数据均符合一级吸收二室模型;血药达峰时间（tp）分别为2.39和4.51 h,血药浓度峰值（Cmax）分别为5.80和5.06 μ.g/mL,消除半衰期（t1/2β）分别为7.25和50.09 h.腹注和口灌给药肌肉、肝脏和肾脏的Cmax分别为2.504和2.678 μ g/g、4.612和4.393 μg/g、12.464和7.509 μg/g,tp分别为6.0和4.0h、2.0和4.0h、1.5和4.0h;甲砜霉素在红笛鲷体内消除速度较慢,肌肉、肝脏和肾脏的t1/2β分别为37.168和33.519 h、22.499和33.649 h、19.672和8.673 h.结果表明：腹注给药方式下甲砜霉素在红笛鲷体内的吸收快于口灌给药,在血浆和肝脏中的消除快于口灌给药,在肌肉和肾脏中的消除则慢于口灌给药.     

妊娠绵羊安氟醚药代动力学研究

本文应用气相色谱测定妊娠绵氟醚吸入麻醉期间血药浓度和终末吸气浓度，并研究了安氟醚在妊娠绵羊体内药代动力学过程。经适当动力学模型的建立，分别描述具动力学特点，药代动力学研究表明：安氟醚在妊娠绵羊体内血液药物浓度时间规律为：Ｃ＝１２．４８３２９（ｅ＾－０．０３４４９６４ｔ－ｅ＾－０．０３２６２４２３ｔ）安氟醚吸入后药时曲线符合一级吸收一室开放性模型。动力学参数分别为：消除相生物半衰期（ｔ１／２β）＝２     

二甲苯胺噻唑在绵羊脑脊液中的药物动力学研究

以内标气相色谱法为定量手段，研究二甲苯胺噻唑在绵羊脑脊液（ＣＳＦ）中的药动力学。实验结果表明，绵羊肌注二甲苯胺噻唑（２．５ｍｇ／ｍｌ）后，ＣＳＦ药物经时特征主要符合一级吸收单室开放模型，部分符合一级吸收双室开放模型，其主要药动学参数：吸收半衰期为３．８６８±１．４５２ｍｉｎ，消除半衰期为１４０．３３８±１１０．０３８ｍｉｎ，ＣＳＦ药浓度达峰时间为１７．６３７±５．８５０ｍｉｎ，ＣＳＦ药峰浓度为０．     

环丙沙星和磺胺二甲嘧啶在大菱鲆体内的药代动力学比较

采用高效液相色谱法,在(23.1±0.8)℃水温条件下,对环丙沙星和磺胺二甲嘧啶两种抗菌药物在健康大菱鲆体内的代谢动力学规律进行了比较研究。结果显示,单次口服环丙沙星和磺胺二甲嘧啶后,药物在血浆中的经时过程均符合一级吸收二室开放模型,表达方程分别为CCIP=14.811e-0.337t+4.028e-0.063t-18.839e-0.616t、CSM2=64.981e-0.141t+4.59e-0.004t-69.571e-0.19t;静脉注射这两种药物后,药物在血浆中经时过程均符合无级吸收二室开放模型,表达方程分别为CCIP=21.784e-1.098t+1.514e-0.043t、CSM2=33.028e-5.687t+8.674e-0.013t。口服相同剂量(20 mg/kg)药物后,对血浆的药代动力学参数进行比较,环丙沙星的Tmax(6 h)、Cmax(5.385μg/mL)、t1/2Ka(1.125h)、t1/2α(2.057 h)和t1/2β(11.028 h)均小于磺胺二甲嘧啶给药(8 h、13.990μg/mL、3.647 h、4.923 h和173.407 h),且F(60.57%)大于磺胺二甲嘧啶给药F(47.13%)。证实环丙沙星在大菱鲆体内的吸收、分布、消除速度,达峰时间均快于磺胺二甲嘧啶给药,且比磺胺二甲嘧啶给药吸收完全。根据本实验的结果,环丙沙星和磺胺二甲嘧啶的合理给药方案分别为28.01 mg/kg和18.32 mg/kg,均为每日1次给药,连用3～5 d。     

Pharmacokinetics, safety and tissue residues of sustained-release sulfamethazine in sheep

Concentration-time profiles and the rates of absorption, extent of distribution and half-lives of sulfamethazine (SMZ), administered intravenously, orally as a water solution and as a sustained-release formulation (CalfSpan) were determined in 10 healthy sheep. The geometric mean half-life of elimination of i.v. SMZ was 10.8 h, compared to 14.3 h for the sustained-release preparation (CalfSpan) and 4.3 h for the oral water solution. Blood levels of SMZ were at or above 50 micrograms/ml for more than 48 h for CalfSpan, for 24 h after i.v. SMZ (100 mg/kg body wt), and for less than 24 h after p.o. SMZ (100 mg/kg body wt). The mean bioavailability of the oral SMZ solution was 58.3% (AUCp.o./AUCi.v.). The estimated bioavailability of the CalfSpan preparation was 52.5%. The safety of the sustained-release preparation was tested by dosing sheep with multiples (one, three and five times) of the recommended dose (one tablet, 8 g SMZ, per 20 kg body wt), once a day for 3 days. Clinical blood chemistries showed a significant increase in serum iron, and a decrease in serum phosphorus in animals treated at the 3x and 5x dose levels. Necropsies of the 5x dose animals did not show any gross signs that could be attributed to SMZ, and histological examination of tissues from the 5x animals revealed no organ pathology. Residues of SMZ in liver, fat, kidney and skeletal muscle were measured in 20 animals that received one bolus per 20 kg body wt. The results indicate that SMZ residues are cleared rapidly, and are at or below the tolerance level of 0.1 mg/kg within 8 days after dosing so that the 18-day withdrawal time used in cattle would provide an appropriate margin of safety if used in sheep.     

Pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous and oral administration in goats

Summary

The intravenous and oral pharmacokinetics of an amoxicillin and clavulanic acid combination (20 mg/kg of sodium amoxicillin and 5 mg/kg of potassium clavulanate) were studied in six goats. After intravenous administration the pharmacokinetics of both drugs could be described by an open two‐compartment model. Amoxicillin had a greater distribution volume (0.19 ± 0.01 l/kg) than clavulanic acid (0.15 ± 0.01 l/kg), whereas the distribution and elimination constants were higher for the latter, which was eliminated more quickly than amoxicillin. After oral administration of both drugs their pharmacokinetic behaviour was best described by an open one‐compartment model with first‐order absorption. Elimination half‐lives were twice as long after oral (2.15 ± 0.20 h and 1.94 ± 0.16 h for amoxicillin and clavulanic acid respectively) than after intravenous administration (1.20 ± 0.16 h and 0.86 ± 0.09, respectively). An apparent ‘flip‐flop’ situation was evident in this study. Bioavailability was 27% for amoxicillin and 50% for clavulanic acid.     

Disposition kinetics of enrofloxacin (Baytril 5%) in sheep and goats following intravenous and intramuscular injection using a microbiological assay

The pharmacokinetics of enrofloxacin were determined in Desert sheep and Nubian goats after intravenous and intramuscular administration of Baytril at the dose of 5mgkg(-1) bodyweight. A two compartment open model best represented the intravenous plasma concentration versus time data in both species. Comparisons between the means of the pharmacokinetic parameters obtained after intravenous administration of enrofloxacin (Baytril) revealed a significantly smaller distribution rate constant (lambda(1)) and consequently a shorter half-life time of distribution in sheep (P<0.05). A larger volume of the central compartment (Vc) was observed in goats (P<0.05). Similar values were obtained for sheep and goats for the remaining parameters.Plasma concentrations versus time data of enrofloxacin after 5mgkg(-1) intramuscular administration of Baytril in sheep and goats were adequately described by one-compartment open model with first order absorption and elimination. There were no significant differences between sheep and goats in any of the estimated pharmacokinetic parameters.The results indicate that the pharmacokinetics of enrofloxacin did not differ significantly between sheep and goats; similar intravenous and intramuscular dose rates of enrofloxacin should therefore be applicable to both species. Owing to the high variations in MIC (minimal inhibitory concentration) of sensitive veterinary pathogens, it is recommended that enrofloxacin dosage regimens be calculated according to the sensitivity of the individual pathogen, site of infection and clinical response, than by following a preset dosage regimen.     

持续染毒后硝基苯在奶牛尿液中的代谢动力学研究

本文以高效液相色谱（High Performance Liquid Chromatography,HPLC）作为硝基苯在奶牛体内主要代谢产物的定量手段,采用MCPKP自动化药动学分析程序分析其浓度-时间数据,以不同剂量硝基苯,通过奶牛自由饮水持续经口染毒,分别研究了硝基苯的三种主要代谢产物氨基酚、硝基苯胺和硝基酚在奶牛尿液中的动态变化规律和残留消除规律。结果表明,奶牛尿液中只有代谢产物氨基酚,说明动物染毒硝基苯后,氨基酚是尿中唯一的高剂量排泄物,并且氨基酚浓度随时间而变化的规律符合一级吸收一室模型。     

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.     

盐酸环丙沙星在患子宫内膜炎奶牛子宫内给药的药物浓度

本研究以反相高效液相色谱为定量分析手段，选用5头患子宫内膜炎的奶牛，通过子宫内灌注盐酸环丙沙星（2.5 g/头），研究了盐酸环丙沙星在患子宫内膜炎奶牛体内的药物动力学规律。以二氟沙星为内标，血浆样品经甲醇沉淀蛋白，离心，经针头式过滤器处理，用反相高效液相法测定其中盐酸环丙沙星的浓度。 色谱条件为：ODS-1C₁₈柱；测定流动相为0.015 mol/L四丁基溴化铵溶液-乙腈（92∶8，V/V），pH为3.0；流速为1.0 ml/min；荧光检测器，激发波长（λex）278 nm，发射波长（λem）465 nm。通过采用MCPKP房室分析程序，分析血中浓度 时间数据，发现有3头奶牛血样药时数据符合无吸收三室开放模型。其血样中主要药动学参数为：T_1/2α为0.916 h、T_1/2β为49.20 h、AUC高达7.6296 mg/L·h、Clβ为1.582 L/kg·h，β为0.642 h^-1。有2头奶牛血样药时数据符合一级吸收二室开放模型。其主要药动学参数为：T_1/2α为1.26 h、T_1/2β为9.2 h、AUC高达28.336 mg/L·h，β为0.3571 h^-1。试验结果表明，盐酸环丙沙星子宫给药吸收快，分布广，消除慢。     

Nonlinear mixed effects pharmacokinetic/pharmacodynamic analysis of the anticonvulsant ameltolide (LY201116) in a canine seizure model

The anticonvulsant ameltolide (LY201116) is a novel potential therapy for the treatment of canine epilepsy. Eight dogs were administered five different oral doses of ameltolide and clinical scoring of the maximal electroshock (MES) induced seizures at 3 and 24 h postdosing were determined in two separate crossover design studies. Plasma ameltolide concentrations were determined at the time of seizures in all dogs and complete plasma concentration‐time profiles were also determined in a separate study. A nonlinear mixed effects PK/PD model was fit to the resulting data. A one compartment open model with first order absorption was determined to best fit the ameltolide pharmacokinetics. An effect compartment with a cumulative logistic regression equation was used to establish the PK/PD relationship. The mean bioavailability normalized volume of distribution and the elimination half‐life were estimated at 1.20 L/kg and 5.46 h, respectively. The fitted model estimated that from 2 to 15 h following a single 3 mg/kg oral ameltolide dose the mean probability of obtaining a 1 unit reduction in the seizure clinical score severity was greater than 0.80. The utilized PK/PD analysis combined with the canine MES model allowed for the rapid and efficient determination of the plasma ameltolide concentration‐anticonvulsant relationship preclinically in dogs.     

Determination of influence of food intake after a single oral dose of mosapride in beagle dogs using nonlinear mixed effect modeling

The objective of this study was to describe the population pharmacokinetics (PK) of mosapride under fasting and fed conditions. A single 5‐mg oral dose of mosapride was administered to fasted (n = 15) and fed (n = 12) beagle dogs. Plasma concentrations of mosapride were subsequently measured by liquid chromatography–tandem mass spectrometry. Data were analyzed using modeling approaches with the NONMEM 7.2 software. A one‐compartment open PK model utilizing model event time (MTIME) with first‐order absorption and first‐order elimination was found to be more appropriate than all other PK models tested. The absorption rate constants of mosapride were significantly decreased under fed conditions, compared to fasting conditions. The observed bootstrap medians of PK parameters were generally consistent with the corresponding population mean estimates. Furthermore, with the exception of some mosapride concentrations, most of observed data fell into the range of the 5th and 95th percentiles of the simulated values. Overall, the final model was able to describe the observed mosapride concentrations reasonably well. These findings suggest that food intake affects both the rate and extent of absorption of mosapride and that the pharmacological effect of mosapride can differ significantly depending on food intake.     

Comparison of florfenicol pharmacokinetics in Exopalaemon carinicauda at different temperatures and administration routes

Florfenicol is a broad‐spectrum antibacterial drug. Exopalaemon carinicauda is important in the prawn aquaculture industry in China. Florfenicol pharmacokinetics in E. carinicauda were studied at different temperatures and via different routes of administration to provide a scientific basis for the rational use of drugs for E. carinicauda production. At water temperatures of 22 ± 0.4°C and 28 ± 0.3°C, after intramuscular (IM) injection and oral (per ora (PO)) administration of florfenicol at 10 mg/kg body weight (BW) and 30 mg/kg BW, respectively, the florfenicol concentration in the plasma, hepatopancreas, gills, muscles, and carapace of E. carinicauda was determined by high‐performance liquid chromatography. After IM injection at different temperatures, the metabolism of florfenicol in E. carinicauda conformed to a two‐compartment open model with zero‐order absorption. After PO administration, the metabolism of florfenicol in E. carinicauda was consistent with a two‐compartment open model with first‐order absorption. Using an identical administration route but different water temperatures, the metabolism of florfenicol in E. carinicauda was quite different. Overall, florfenicol was absorbed rapidly and distributed widely in E. carinicauda, but elimination was slow and the bioavailability was not high. A low temperature and PO administration resulted in a low elimination rate.     

Use of pharmacokinetics to predict the distribution of pantothenate in dogs.

On the basis of plasma concentrations of pantothen[14C]ate, after its intravenous administration, a three compartment open model was proposed to predict the pharmacokinetics of pantothenate in dogs. The model assumed a central compartment comprising the plasma and other extracellular fluids, and distribution into two other peripheral compartments, one of which included the liver. Elimination of unchanged pantothenate was assumed to occur by metabolism from the compartment which included the liver. Distribution of pantothen[14C]ate from the plasma compartment into the liver compartment was shown to be very rapid; during 10 min after intravenous administration about 80 per cent of the dose had been cleared from the plasma compartment. The model successfully predicted the influence (first pass effect) of the liver on the fraction of an oral dose which reached the peripheral plasma unchanged.