牛蒡子中牛蒡苷元在仔猪体内的药物动力学研究

为研究牛蒡子粉在仔猪体内的药物动力学特征,了解其在仔猪体内的吸收、分布、转化和排泄规律,为新兽药的研发和临床用药提供理论参考依据。选取健康仔猪8头(30.0±5.0kg),以1.0g/kg.bw的牛蒡子粉灌胃给药,不同时间点前腔静脉采血,采用HPLC法对猪血浆中牛蒡苷元的浓度进行分析。牛蒡子粉灌胃给药后,符合有吸收二室模型,主要药物动力学参数为：吸收半衰期(t_1/2ka)为0.274±0.102 h,分布半衰期(t_1/2α)1.435±0.725h;消除半衰期(t_1/2β)63.467±29.115 h;表观分布容积(V_d)1.680±0.402 L/kg;清除率(CL_b)0.076±0.028L/(h.kg);达峰时间(t_max)为0.853±0.211 h,峰浓度(c_max)为0.430±0.035μg /mL,药时曲线下面积(AUC)14.672±4.813μg.h/mL。试验表明：牛蒡子粉口灌后在仔猪体内吸收迅速、分布广泛、代谢消除缓慢,能够较长时间发挥药理作用。     

牛蒡子粉中牛蒡苷元在仔猪体内的药物动力学研究

为研究牛蒡子粉中牛蒡苷元在仔猪体内的药物动力学特征,了解其在仔猪体内的吸收、分布、转化和排泄规律,为新兽药的研发和临床用药提供理论参考依据。选取健康仔猪8头(30.0±5.0 kg),以1.0 g/kg·bw的牛蒡子粉灌胃给药,不同时间点前腔静脉采血,采用HPLC法对猪血浆中牛蒡苷元的浓度进行分析。牛蒡子粉灌胃给药后,符合有吸收二室模型,主要药物动力学参数为:吸收半衰期(t_(1/2 ka))为0.274±0.102 h,分布半衰期(t_(1/2α))1.435±0.725 h;消除半衰期(t_(1/2β))63.467±29.115 h;表观分布容积(V_d)1.680±0.402 L/kg;清除率(CL_b)0.076±0.028 L/(h·kg);达峰时间(t_(max))为0.853±0.211 h,峰浓度(c_(max))为0.430±0.035μg/mL,药时曲线下面积(AUC)14.672±4.813μg·h/mL。试验表明:牛蒡子粉口灌后牛蒡苷元在仔猪体内吸收迅速、分布广泛、代谢消除缓慢,能够较长时间发挥药理作用。     

健康仔猪单剂量内服左旋氧氟沙星的药动学研究

以20mg/kg剂量内服进行左旋氧氟沙星的辩证药动学研究。高效液相色谱法测定血浆药物浓度、3P97药代动力学程序处理药时数据。健康组药时数据符合一级吸收一室模型,其主要药动学参数为:吸收半衰期t1/2ka(0.42±0.08)h,消除半衰期t1/2ke(7.62±0.38)h,达峰时间tmax(1.85±0.25)h,峰浓度Cmax(6.99±0.92)mg/L,药时曲线下面积AUC(90.7±10.07)mg/L·h,生物相表观分布容积VF(s)(2.45±0.28)L/kg,平均滞留时间MRT(11.92±0.94)h。     

国产表阿佛菌素在绵羊体内的药代动力学研究

用反相高效液相色谱结合荧光检测法,对试验绵羊经静脉、皮下单剂量注射0 2 mg/kg表阿佛菌素的药代动力学进行了研究。血样提取物通过C18小柱富集、洗脱,甲醇洗提部分经加入1 甲基咪唑和三氟乙酸酐的乙腈液衍生化后进行色谱分析。血药浓度在 2. 5 ~ 200 ng/mL 范围呈良好线性关系(R= 0 996 8),方法平均回收率96 65%±3.84%,血药最低检测限 2.5 ng/mL,日内、日间变异系数分别小于 10%、12%。2 种途径给药后体内药物运转分别符合二室和一室开放模型。主要药代参数如下,静脉注射:消除半衰期(T1/2β)12.66±2.05 h,药时曲线下面积(AUC0~74)1.02±0 30 (mg/L)·h,fc=0 13±0 05; 皮下注射:吸收半衰期(T1/2ka )4.42±1.04 h,峰浓度(Cmax)0 02±0 01 μg/mL,峰时(Tmax ) 15. 36±2. 91 h,消除半衰期(t1/2k ) 26. 22±9. 04 h,药时曲线下面积(AUC0~122)1.19±0 37 (mg/L)·h。上述结果表明,绵羊静脉注射表阿佛菌素后体内药物分布广泛,消除较慢。皮下注射吸收好,消除比静脉注射更为缓慢,体内药物平均滞留时间长。     

仔猪脾虚状态下单剂量口服左旋氧氟沙星的药动学研究

10头健康仔猪随机均分为健康组、脾虚组 ,按 2 0mg/kg的剂量进行内服左旋氧氟沙星的药动学研究。高效液相色谱法测定血浆中药物浓度 ,3P97药代动力学程序处理药时数据。健康组和脾虚组药动学数据适合一级吸收一室模型。健康组主要药动学数据为 :吸收半衰期 (t1 / 2ka)(0 42± 0 0 8)h ,消除半衰期 (t1 / 2ke) (7 62± 0 38)h ,达峰时间 (tmax) (1 85± 0 2 5)h ,达峰浓度 (Cmax) (6 99± 0 92 )mg/L ,药时曲线下面积 (AUC) (90 7± 1 0 0 7)mg·L- 1 ·h ,表观分布容积 (V/ F(s) ) (2 45± 0 2 8)L·kg,平均滞留时间 (MRT) (1 1 92± 0 94)h。脾虚组 :t1 / 2ka(1 1 7± 0 38)h ,t1 / 2ke (9 0 2± 1 1 8)h ,tmax (3 93± 1 0 5)h ,Cmax (4 2 8± 1 45)mg/L ,AUC (72 2 1± 1 6 0 7)mg·L- 1 ·h ,V/ F(s) (3 95±1 2 8)L·kg,MRT (1 3 74± 1 2 1 )h。结果表明 :仔猪脾虚状态下明显影响左旋氧氟沙星内服给药的药动学特征     

黄牛静注、肌注和内服吡喹酮的药动学与生物利用度

6头成年健康黄牛按10 mg/kg剂量单次快速静注吡喹酮,另6头成年健康黄牛根据交叉试验设计法按10 mg/kg剂量单次肌注、30 mg/kg剂量内服吡喹酮进行药动学与生物利用度试验.利用高效液相色谱法测定血浆中吡喹酮原药的质量浓度,其检测限为25μg/L.房室模型分析表明,静注给药后的药时数据符合无吸收二室开放模型,其分布半衰期(t1/2a)、消除半衰期(t1/2β)、表观分布容积(Vd)、总体清除率(ClB)、药时曲线下面积(AUC)分别为(0.25±0.03)h、(1.28±0.20)h、(2.11±0.38)L/kg、(1.14±0.10)L/(kg·h)和(8.79±0.74)mg/(L·h).肌注的药时数据符合有吸收一室开放模型,主要药动学参数吸收半衰期(t 1/2ka)、消除半衰期(t1/2ke)、药时曲线下面积(AUC)、达峰时间(tmax)、峰浓度(Gmax)和生物利用度(F)分别为(0.40±0.17)h、(4.65±0.91) h、(6.85±1.02)mg/(L·h)、(1.33±0.52)h、(0.83±0.08)mg/L和77.93%.内服给药后符合有吸收一室开放模型,吸收不规则,其药动学参数t 1/2ka、t1/2ke、AUC、tmax、Cmax和F分别为(1.08±0.13)h、(6.81±1.26)h、(8.51±1.78)mg/(L·     

美洛昔康片剂在比格犬内的药代动力学及生物利用度研究

本研究以0.1 mg/kg体重的剂量研究美洛昔康片在比格犬中的药代动力学和生物利用度。HPLC分析血浆中的药物浓度,WinNonlin 6.4非房室模型计算药动学参数。比格犬内服美洛昔康片后测得0~48 h美洛昔康的T1/2、Cmax、Tmax和AUC0-t分别为14.55 ± 2.18 h、296.16 ± 74.15 ng·mL-1、6.0 ± 0.00 h和6356.79 ± 1089.78 ng·h·mL-1;比格犬静脉注射美洛昔康溶液后,测得0~48 h美洛昔康的T1/2和AUC0-t分别为11.54 ± 4.18 h和5510.68 ± 1075.29 ng·h·mL-1。内服美洛昔康片剂的绝对生物利用度为115.35%。美洛昔康片在比格犬体内消除速率较慢,消除半衰期较长,在体内滞留时间较长,绝对生物利用度高,药物在体内作用时间较长等药动学特征。     

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。     

肉仔鸡静注和内服环丙沙星(ciprofloxacin)的药物动力学

16只健康 AA肉仔鸡 ,随机分成 2组 ,每组 8只 ,按 10 mg/ kg剂量分别进行静注和内服单剂量环丙沙星药动学试验。血浆中药物浓度用高效液相色谱法测定 ,血药浓度 -时间数据用 MCPKP药动学计算机程序处理。结果表明 ,静注给药后的药时数据符合无吸收二室开放模型 ,主要动力学参数分别为 :t1 /2α为 (0 .2 34± 0 .0 49) h,t1 /2β为 (10 .118±0 .2 71) h,VB为 (1.374± 0 .12 4) L/ kg,CLB为 (0 .0 94± 0 .0 0 9) L· kg- 1 · h- 1 ,AUC为 (10 7.0 6 8± 10 .6 40 ) mg· L- 1· h。内服给药后的药时数据符合一级吸收一室开放模型 ,主要动力学参数分别为 :t1 /2 kα为 (0 .114± 0 .0 0 8) h,t1 /2 k为(7.784± 0 .5 14) h,Tp 为 (0 .70 2± 0 .0 31) h,Cmax为 (5 .736± 0 .5 15 ) m g/ L,AUC为 (6 8.6 2 2± 8.147) mg· L- 1· h,F为 (6 4.0 92± 7.6 10 ) %。肉仔鸡静注环丙沙星在其体内消除较慢 ,分布广泛 ;内服给药吸收迅速 ,消除较静注给药快。     

儿茶素在家兔体内的药物动力学及生物利用度研究

对家兔单剂量静注和灌服儿茶素 (Catechin) 2 5mg/kg体重各 5只。用高效液相色谱法测定其血药浓度。房室模型分析表明静注给药后的药时数据符合无吸收二室开放模型 ,主要动力学参数为 :t1 / 2α=( 0 .1 5± 0 .0 1 )h ,t1 / 2 β=( 0 .5 8± 0 .0 2 )h ,Vc=( 1 .41± 0 .0 8)L ,Vβ=( 2 .97±0 .1 1 )L ,ClB=( 3.5 3± 0 .1 0 )L/h ,AUC =( 1 6.95± 1 .5 2 )mg/(L·h)。灌服儿茶素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为 :t1 / 2Ka=( 0 .39± 0 .0 6)h ,t1 / 2Ke=( 0 .79±0 .1 1 )h ,tmax=( 0 .78± 0 .1 1 )h ,Cmax=( 3.35± 0 .1 6)mg/L ,AUC =( 7.45± 0 .94)mg/(L·h) ,F =( 4 4.1 8± 3.5 9) %。儿茶素在健康家兔体内的药动学特征是 :吸收迅速 ,达峰时间短 ,消除快 ,半衰期短 ,表观分布容积较大 ,口服摄入吸收不完全     

Gentamicin pharmacokinetics in newborn and 42-day-old male piglets

The pharmacokinetics of gentamicin was investigated in six newborn male piglets, aged from 4 to 12 h at the time of administration of the drug, and six 42-day-old castrated male piglets, that had been weaned for 2 weeks following a single intravenous bolus of 5 mg/kg. Gentamicin was measured in serum and in urine by a fluorescence polarization immunoassay. The serum concentrationtime data were best described by a three-compartment open model. A rapid initial distribution phase (± phase) was observed in every animal. The serum β half-life (t_1/2β) was significantly longer in the newborn piglets (mean ± SEM) (5.19 ± 0.30 h) than in the older group (3.50 ± 0.23 h) (P < 0.05). Mean residence time was similarly longer in younger piglets (6.62 ± 0.57 h) than in older animals (2.86 ± 0.11 h) (P < 0.05). The steady-state volume of distribution (V_ills was significantly larger for younger pigs (0.785 ± 0.036 L/kg) than in elder pigs (0.474 ± 0.029 L/kg) (P < 0.05). Urinary γ half-life (t_1/27u) was 72.66 ± 10.78 h in the newborn piglets and 69.20 ± 14.77 h in the 42-day-old animals. A urinary δ phase was observed in three of the 42-day-old piglets and gave a mean (t_1/2δu of 232.01 ± 14.55 h. Percentages of urinary recovery of the administered dose after 144 h were 94.18 ± 1.01 and 94.04 ± 1.12 in the newborn and 42-day-old animals, respectively. Serum gentamicin clearance was significantly lower in younger animals (0.121 ± 0.007 L/h±kg) than in the 42-day-old group (0.166 ± 0.010 L/h·kg). It is suggested that in the newborn piglets, the increase of V_d(ss) could be explained by a higher proportion of extracellular water while the lower clearance could be attributed to a reduced glomerular filtration capacity. Gentamicin dosage requirement in the newborn piglets would therefore have to be adjusted, in order to take into consideration the observed differences in the mean values of these latter pharmacokinetic parameters.     

Pharmacokinetic analysis of cefquinome in healthy chickens

1. The pharmacokinetics of cefquinome (CEQ) in chickens was determined after intravenous (IV) and intramuscular (IM) administration of 2?mg/kg body weight. Plasma concentrations were measured by high performance liquid chromatography assay with an ultraviolet detector at 265?nm wavelength.

2. Plasma concentration–time data after IV administration were best fitted by a two-compartment model. The pharmacokinetic parameters following IV injection were distribution half-life 0·43?±?0·19?h, elimination half-life 1·29?±?0·10?h, total body clearance 0·35?±?0·04?l/kg/h, area under curve 5·33?±?0·55?µg/h/ml and volume of distribution at steady state 0·49?±?0·05?l/kg.

3. Plasma concentration–time data after IM administration were best described by a two-compartment model. The pharmacokinetic parameters after IM administration were absorption half-life 0·07?±?0·02?h, distribution half-life 0·58?±?0·27?h, elimination half-life 1·35?±?0·20?h, peak concentration 3·04?±?0·71?µg/ml and bioavailability 95·81?±?5·81%.

4. Cefquinome kinetics in chicken and data from other species were summarised and analysed to provide a comprehensive understanding of CEQ pharmacokinetics.     

Pharmacokinetics and bioavailability of valnemulin in Muscovy ducks (Cairina moschata)

1. A pharmacokinetic study of valnemulin was conducted in healthy Muscovy ducks after intravenous (IV), intramuscular (IM) and oral administrations at a dose rate of 15?mg/kg body weight.

2. Drug concentrations in plasma were determined by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetics parameters of valnemulin were analysed by compartmental analysis using the WinNonlin program.

3. After IV administration, valnemulin was widely distributed with a volume of distribution based on a terminal phase (V_z) of 8·19?±?3·07?l/kg, a mean elimination half-life (t_1/2Ke) of 2·63?h, and a clearance (Cl) value of 5·56?±?1·53?l/kg/h. Following intramuscular and oral administration, valnemulin was rapidly absorbed; the C_max was 0·44?±?0·13 and 0·12?±?0·02?µg/ml (achieved at 0·28 and 1·80?h), the t_1/2Ke was 3·17?±?3·83 and 4·83?±?1·81?h, and the absolute bioavailability (F) was 72% and 37%, respectively.

4. The plasma profile of valnemulin exhibited favourable pharmacokinetic characteristics in Muscovy ducks, such as wide distribution, and rapid absorption and elimination, though oral bioavailability was low.     

姜黄素固体分散体在猪体内的比较药动学研究

本研究首次建立了测定猪血浆中姜黄素的高效液相色谱串联质谱法（HPLC-MS/MS），比较了在内服给药途径下，姜黄素固体分散体和姜黄素预混剂在仔猪体内的药动学特征。选用16头7周龄左右健康二元杂交猪（约克夏×长白），公母各半，随机分为2组，每组8头，按100 mg·kg^-1（以姜黄素计）分别灌服姜黄素固体分散剂和姜黄素预混剂，不同时间点采集血浆样品，经提取、净化后采用HPLC-MS/MS测定血浆中姜黄素的药物浓度，使用WinNonlin 5.2.1软件非房室模型计算、分析姜黄素在猪体内的药动学参数。结果显示，仔猪灌服姜黄素固体分散体和姜黄素预混剂后的药时曲线下面积（AUC）分别为（104.53±38.67）和（37.82±11.48）h·ng·mL^-1；达峰时间（T_max）分别为（3.25±0.38）和（2.31±0.37）h；峰浓度（C_max）分别为（26.65±9.65）和（9.55±2.75）ng·mL^-1；消除半衰期（t_1/2β）分别为（3.55±2.17）和（6.93±0.86）h；平均驻留时间（MRT）分别为（5.23±0.53）和（4.26±0.47）h，统计分析表明，与预混剂相比，仔猪灌服姜黄素固体分散体后，主要药动学参数差异显著（P<0.01），T_max明显延迟，C_max显著提高，AUC明显增大，姜黄素固体分散体的相对生物利用度为280.39%。结果表明，姜黄素固体分散体可改善姜黄素在肠道的吸收，提高姜黄素的生物利用度，为今后姜黄素固体分散体的开发和临床应用提供科学依据。     

Pharmacokinetics of Curcumin Solid Dispersion in Piglets

A method for the detection of curcumin in pig plasma by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established firstly and the pharmacokinetics of curcumin solid dispersion and curcumin premix in piglets were studied. Sixteen healthy piglets (Yorkshire×Changbai), seven-week aged, half male and half female, were randomly divided into two groups receiving curcumin solid dispersant and curcumin premix orally at the dose of 100 mg·kg^-1, respectively. Then plasma samples were collected at different time points, and the blood concentration of curcumin was determined by HPLC-MS/MS. The WinNonlin 5.2.1 software was used to analyze and calculate the pharmacokinetic parameters. The pharmacokinetic parameters of curcumin solid dispersion and curcumin premix were as follows: the area under the curve (AUC) was (104.53±38.67) and (37.82±11.48) h·ng·mL^-1, time to peak concentration (T_max) was (3.25±0.38) and (2.31±0.37) h, peak concentration (C_max) was (26.65±9.65) and (9.55±2.75) ng·mL^-1, respectively, elimination half-life time (t_1/2β) was (3.55±2.17) and (6.93±0.86) h, mean residence time (MRT) was (5.23±0.53) and (4.26±0.47) h. The statistical analysis showed significant differentce (P<0.01) between curcumin solid dispersion and premix in parameters, the T_max of curcumin solid dispersion was delayed significantly, the C_max was increased obviously and the AUC was improved after the piglets were given curcumin solid dispersion. Compared with curcumin premix, the relative bioavailability of curcumin solid dispersion was 280.39%. The results showed that curcumin solid dispersion could improve the dissolution and absorption of curcumin in the intestinal tract and improve the relative bioavailability of curcumin, which provided a scientific basis for the development and clinical application of curcumin solid dispersions in the future.     

Pharmacokinetics and bioavailability of cefquinome in healthy piglets

A study on bioavailability and pharmacokinetics of cefquinome in piglets was conducted after intravenous (i.v.) and intramuscular (i.m.) administrations of 2.0 mg/kg of body weight, respectively. Plasma concentrations were measured by high‐performance liquid chromatography assay with UV detector at 268‐nm wavelength. Plasma concentration–time data after i.v. administration were best fit by a two‐compartment model. The pharmacokinetic values were distribution half‐life 0.27 ± 0.21 h, elimination half‐life 1.85 ± 1.11 h, total body clearance 0.26 ± 0.08 L/kg·h, area under curve 8.07 ± 1.91 μg·h/mL and volume of distribution at steady state 0.46 ± 0.10 L/kg. Plasma concentration–time data after i.m. administration were also best fit by a two‐compartment model. The pharmacokinetic parameters were distribution half‐life 0.88 ± 0.42 h, elimination half‐life 4.36 ± 2.35 h, peak concentration 4.01 ± 0.57 μg/mL and bioavailability 95.13 ± 9.93%.     

克蚕菌的药物动力学研究

采用微生物法测定 5龄健康家蚕食下克蚕菌后的经时过程血药浓度。用药物动力学软件结合EXCEL程序拟和计算 ,克蚕菌在蚕体内的血药浓度—时间曲线符合一级吸收动力学和单室模型特征。其血药浓度随时间变化的单室模型关系式为C =16 .6 2 87(e-0 119t-e-0 742t) ,实测血药浓度—时间曲线与理论血药浓度—时间曲线的相关系数R2 =0 .96 33。求得克蚕菌的药物动力学参数分别为 :ka=(0 .74 2± 0 .12 3) /h ;k =(0 .119± 0 .0 0 3) /h ;t1/ 2 (a)=(0 95 8± 0 180 )h ;t1/ 2 =(5 82 1± 0 15 3)h ;Cmax=(9 70 7± 0 16 3) μg/mL ;Tmax=(2 .971± 0 .32 2 )h ;VD=(0 .5 4 3± 0 .0 2 5 )L ;CL =(0 .0 6 5± 0 .0 0 1)L/h ;AUC =(117.5 0 3± 3.30 6 )h·(μg/mL)。     

硫酸头孢喹肟在鸭体内的药动学及生物利用度研究

试验将20只2月龄健康番鸭,随机分为2组,每组10只,雌雄各半,分别进行静脉注射和口服硫酸头孢喹肟给药的药动学研究。静脉注射和口服的给药剂量分别为10和20 mg/kg。以反相HPLC测定血浆中硫酸头孢喹肟的浓度,血药浓度—时间数据用3P97药动学程序软件处理。鸭单剂量静脉注射给药后,血药浓度—时间数据符合无吸收二室开放模型,其主要动力学参数分别为:V（c）,（1.146±0.02） L/kg;t_1/2α,（0.290±0.02）h;t_1/2β,（1.691±0.15）h;AUC （6.635±0.18）（mg·h）/L;CL（s）,（1.508±0.04）L/（kg·h）。鸭口服硫酸头孢喹肟的血药浓度—时间数据符合一级吸收一室开放模型,主要动力学参数分别为:t_1/2（ka）,（0.45±0.05）h;t_1/2（ke）,（0.96±0.29）h;T_（peak）,（0.91±0.09）h;C_（max）,（3.14±0.64）mg/L;AUC,（8.29±1.26）（mg·h）/L;F,（62.55±0.10）%。硫酸头孢喹肟在体内的药动学特征表现为吸收迅速、分布广泛、消除迅速。但口服给药在鸭体内生物利用度低,可能由于硫酸头孢喹肟的脂溶性低,其在消化道吸收率低所致。但8 h内能保持有效血药浓度范围（（0.14±0.03）~（3.14±0.64）μg/mL）,可抑制鸭疫里默氏杆菌及其他细菌感染。