Pharmacokinetics and ex vivo pharmacodynamics of cefquinome in porcine serum and tissue cage fluids

A tissue cage (TC) model was used to evaluate the pharmacokinetics and ex vivo pharmacodynamics of cefquinome after intravenous (IV) and intramuscular (IM) administration to piglets at 2 mg/kg bodyweight. The mean values of area under the concentration–time curve (AUC) were 21.28 (IV) and 21.37 (IM) μg h/mL for serum, and 17.40 (IV) and 16.57 (IM) μg h/mL for TC fluid (TCF), respectively. Values of maximum concentration (C_max) were 6.15 μg/mL (serum) and 1.15 μg/mL (TCF) after IM administration. The elimination half-lives (t_1/2β) in TCF (10.63 h IV and 11.81 h IM) were significantly higher than those in serum (2.33 h IV and 2.30 h IM) (P < 0.05). The values of AUC_TCF/AUC_serum (%) after IV and IM administration were 82.4% and 80.7%, respectively.The ex vivo time-kill curves were established for serum and TCF samples using Escherichia coli ATCC 25922. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values of cefquinome against E. coli were 0.030 and 0.060 μg/mL in Mueller–Hinton broth, and 0.032 and 0.064 μg/mL in both serum and TCF, respectively. The ex vivo growth inhibition data of TCF after IM administration were fitted to the sigmoid E_max model; AUC_24h/MIC was 35.01 h for bactericidal activity and 44.28 h for virtual eradication, respectively. The findings from this study suggest that cefquinome may be therapeutically effective in diseases of pigs caused by E. coli when used at a dose rate of 1.33 mg/kg administered every 24 h for organisms with MIC₉₀ ⩽ 0.50 μg/mL.     

Pharmacokinetics and tissue residues of enrofloxacin in the largemouth bass (Micropterus salmoides) after oral administration

The study was carried out to evaluate the pharmacokinetic disposition of enrofloxacin (ENF) with a single dose of 20 mg/kg after oral administration in largemouth bass (Micropterus salmoides) at 28°C. The concentrations of ENF and of its metabolite ciprofloxacin (CIP) in plasma, liver, and muscle plus skin in natural proportions were determined using HPLC. The concentration–time data for ENF in plasma were best described by a two-compartment open model. After oral administration, the maximum ENF concentration (C_max) of 10.99 μg/ml was obtained at 0.60 hr. The absorption half-life (T_1/2Ka) of ENF was calculated to be 0.07 hr whereas the elimination half-life (T_1/2β) of the drug was 90.79 hr. The estimates of area under the plasma concentration–time curve (AUC) and apparent volume of distribution (Vd/F) were 1,185.73 μg hr/ml and 2.21 L/kg, respectively. ENF residues were slowly depleted from the liver and muscle plus skin of largemouth bass with the T_1/2β of 124.73 and 115.14 hr, respectively. Very low levels of ciprofloxacin were detected in the plasma and tissues. A withdrawal time of 24 days was necessary to ensure that the residues of ENF + CIP in muscle plus skin were less than the maximal residue limit (MRL) of 100 μg/kg established by the European Union.     

Pharmacokinetics and pharmacodynamics of hydromorphone hydrochloride in healthy horses

ObjectivesTo determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses.Study designProspective, randomized, crossover study.AnimalsA group of six adult healthy horses weighing 585.2 ± 58.7 kg.MethodsEach horse was administered IV hydromorphone (0.025 mg kg^–1; treatment H0.025), hydromorphone (0.05 mg kg^–1; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was totaled over 24 hours. Data were analyzed using repeated measures anova with significance at p < 0.05. Blood samples were collected in treatment H0.05 for quantification of plasma hydromorphone and hydromorphone-3-glucuronide and subsequent pharmacokinetic parameter calculation.ResultsHydromorphone administration resulted in a dose-dependent increase in heart rate (HR) and systolic arterial pressure (SAP). HR and SAP were 59 ± 17 beats minute^–1 and 230 ± 27 mmHg, respectively, in treatment H0.05 at 5 minutes after administration. No clinically relevant changes in respiratory rate, arterial gases or temperature were observed. The borborygmi scores in both hydromorphone treatments were lower than baseline values for 2 hours. Fecal output did not differ among treatments and no evidence of abdominal discomfort was observed. Recorded behaviors did not differ among treatments. For hydromorphone, mean ± standard deviation for volume of distribution at steady state, total systemic clearance and area under the curve until the last measured concentration were 1.00 ± 0.29 L kg^–1, 106 ± 21 mL minute^–1 kg^–1 and 8.0 ± 1.5 ng hour mL^–1, respectively.Conclusions and clinical relevanceHydromorphone administered IV to healthy horses increased HR and SAP, decreased abdominal borborygmi and did not affect fecal output.     

超高效液相色谱-串联质谱法测定鸡组织中泰乐菌素的残留量

建立了鸡组织中泰乐菌素残留的超高效液相色谱-串联质谱法检测方法,样品用甲醇(含2%氨水)提取,经C18固相萃取柱净化,洗脱液氮气吹干,残渣用甲醇:乙腈(20∶80,V/V)复溶,超高效液相色谱-串联质谱法检测,基质添加标准溶液外标法定量。结果表明泰乐菌素在5~1000μg/kg的浓度范围内呈现良好的线性关系。在鸡组织中中泰乐菌素的检测限为4μg/kg,定量限为10μg/kg。在10~200μg/kg添加浓度范围内,泰乐菌素在鸡组织中的回收率均在85.9%~110.4%之间,批内批间变异系数在1.2%~4.0%之间。该方法各项技术指标均能满足残留检测要求,且方法的重现性良好,满足国内外兽药残留相关法规规定。     

Pharmacokinetics and pharmacodynamics of hydromorphone after intravenous and intramuscular administration in horses

ObjectiveTo compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration.Study designRandomized, masked, crossover design.AnimalsA total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg.MethodsHorses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg^⁻1 IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg^⁻1 IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for 24 hours after treatments. Pharmacodynamic data were collected for 24 hours after treatments. Variables included thermal nociceptive threshold, heart rate (HR), respiratory frequency (f_R), rectal temperature, and fecal weight. Data were analyzed using mixed-effects linear models. A p value of less than 0.05 was considered statistically significant.ResultsThe mean ± SD hydromorphone terminal half-life (t_1/2), clearance and volume of distribution of H-IV were 19 ± 8 minutes, 79 ± 12.9 mL minute^⁻1 kg^⁻1 and 1125 ± 309 mL kg^⁻1. The t_1/2 was 26.7 ± 9.25 minutes for H-IM. Area under the curve was 518 ± 87.5 and 1128 ± 810 minute ng mL^⁻1 for H-IV and H-IM, respectively. The IM bioavailability was 217%. The overall thermal thresholds for both H-IV and H-IM were significantly greater than P (p < 0.0001 for both) and baseline (p = 0.006). There was no difference in thermal threshold between H-IV and H-IM. No difference was found in physical examination variables among groups or in comparison to baseline. Fecal weight was significantly less than P for H-IV and H-IM (p = 0.02).Conclusions and clinical relevanceIM hydromorphone has high bioavailability and provides a similar degree of antinociception to IV administration.IM hydromorphone in horses provides a similar degree and duration of antinociception to IV administration.     

Pharmacokinetics and pharmacodynamics of intravenous medetomidine in the horse

ObjectiveTo describe the pharmacodynamics and pharmacokinetics following an intravenous (IV) bolus dose of medetomidine in the horse.Study designProspective experimental trial.AnimalsEight, mature healthy horses age 11.7 ± 4.6 (mean ± SD) years, weighing 557 ± 54 kg.MethodsMedetomidine (10 μg kg^?1) was administered IV. Blood was sampled at fixed time points from before drug administration to 48 hours post administration. Behavioral, physiological and biochemical data were obtained at predetermined time points from 0 minutes to 24 hours post administration. An algometer was also used to measure threshold responses to noxious stimuli. Medetomidine concentrations were determined by liquid chromatography-Mass Spectrometry and used for calculation of pharmacokinetic parameters using noncompartmental and compartmental analysis.ResultsPharmacokinetic analysis estimated that medetomidine peaked (8.86 ± 3.87 ng mL^?1) at 6.4 ± 2.7 minutes following administration and was last detected at 165 ± 77 minutes post administration. Medetomidine had a clearance of 39.6 ± 14.6 mL kg^?1 minute^?1 and a volume of distribution of 1854 ± 565 mL kg^?1. The elimination half-life was 29.1 ± 12.5 minutes. Glucose concentration reached a maximum of 176 ± 46 mg dL^?1 approximately 1 hour post administration. Decreased heart rate, respiratory rate, borborygmi, packed cell volume, and total protein concentration were observed following administration. Horses lowered their heads from 107 ± 12 to 20 ± 10 cm within 10 minutes of drug administration and gradually returned to normal. Horse mobility decreased after drug administration. An increased mechanical threshold was present from 10 to 45 minutes and horses were less responsive to sound.Conclusion and clinical relevance Behavioral and physiological effects following intravenous administration positively correlate with pharmacokinetic profiles from plasma medetomidine concentrations. Glucose concentration gradually transiently increased following medetomidine administration. The analgesic effect of the drug appeared to have a very short duration.     

Pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites in horses after intravenous administration of four doses

The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total protein were also assessed. Morphine‐3 glucuronide (M3G) was the predominant metabolite detected, with concentrations exceeding those of morphine‐6 glucuronide (M6G) at all time points. Maximal concentrations of M3G and M6G ranged from 55.1 to 504 and 6.2 to 28.4 ng/ml, respectively, across dose groups. The initial assessment of morphine pharmacokinetics was done using noncompartmental analysis (NCA). The volume of distribution at steady‐state and systemic clearance ranged from 9.40 to 16.9 L/kg and 23.3 to 32.4 ml min^?1 kg^?1, respectively. Adverse effects included signs of decreased gastrointestinal motility and increased central nervous excitation. There was a correlation between increasing doses of morphine, increases in M3G concentrations, and adverse effects. Findings from this study support direct administration of purified M3G and M6G to horses to better characterize the pharmacokinetics of morphine and its metabolites and to assess pharmacodynamic activity of these metabolites.     

Pharmacokinetics of subcutaneously administered doramectin in alpacas

The objective of this research was to evaluate comparative pharmacokinetics of doramectin in alpacas, after subcutaneous administration of 0.2 mg/kg dose. Six healthy adult alpacas, mean age of 5 years ± 1, (three female and three gelded males) of mean bodyweight of 62 kg ± 16 kg with an average body condition scored 2.8 ± 1 out of five, were used in this study. Serial blood samples were collected from the jugular vein before the administration until day 21 afterwards to establish the pharmacokinetics of doramectin after its subcutaneous administration at 0.2 mg/kg dose. The blood samples were analysed using high-performance liquid chromatography (HPLC), fluorescence detection method with precolumn derivatisation, validated for alpacas. The pharmacokinetic parameters were calculated using a noncompartmental model, and results showed Cmax (6.05 ± 5.34 ng/ml), Tmax (3.83 ± 2.48 days), AUC (62.12 ± 18.86 ng/ml × d), terminal half-life (6.2 ± 4.9 days) and MRT (11.56 ± 4.43 days). The results of this study showed that the Cmax and AUC were much lower than in cattle and sheep at the same dosage. Tmax remained similar to cattle and sheep. This study presents valuable information about pharmacokinetics of doramectin in alpacas, which can be utilised in its future efficacy studies.     

三聚氰胺在中华鳖组织中的代谢动力学研究

应用液相色谱-串联质谱监测技术研究了三聚氰胺药饵多次给药后在中华鳖体内的药物代谢动力学。结果表明,中华鳖血液、肝脏、肌肉中三聚氰胺浓度分别在8、4、2h时达到高峰;最高峰时血液、肝脏、肌肉中药物质量浓度平均分别为16.98、16.79和12.05mg/kg。在血液、肝脏和肌肉组织中三聚氰胺浓度的t1/2（ke）分别为24.11、107.75和36.49h。三聚氰胺在血液、肝脏、肌肉组织中的代谢过程均符合一室模型,相应的动力学方程分别为：C血液=17.08×（e-0.0287t-e0.0558t）,C肌肉=11.64×（e-0.0190t-e2.1425t）,C肝脏=15.72×（e-0.0064t-e2.5558t）。说明药饵给药后三聚氰胺在中华鳖体内消除较慢。     

Pharmacokinetics of florfenicol and thiamphenicol in ducks

The pharmacokinetics of florfenicol (FF) and thiamphenicol (TP) after single intravenous (IV) and oral (PO) administration was investigated in Mulard ducks. Both antibiotics were administered at a dose of 30 mg/kg body weight, and their concentrations in plasma samples were assayed using high‐performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were calculated using a noncompartmental method. After IV administration, significant differences were found for the mean residence time (2.25 ± 0.21 hr vs. 2.83 ± 0.50 hr for FF and TP, respectively) and the general half‐life (1.56 ± 0.15 hr vs. 1.96 ± 0.35 hr for FF and TP, respectively) indicating slightly slower elimination of TP as compared to FF. The clearance, however, was comparable (0.30 ± 0.07 L/hr/kg for FF and 0.26 ± 0.04 L/hr/kg for TP). The mean volume of distribution was below 0.7 L/kg for both drugs. Pharmacokinetics after PO administration was very similar for FF and TP suggesting minor clinical importance of the differences found in the IV study. Both antimicrobials showed rapid absorption and bioavailability of more than 70% indicating that PO route should be an efficient method of FF and TP administration to ducks under field conditions.     

Pharmacokinetics and pharmacodynamics of alfaxalone after a single intramuscular or intravascular injection in mallard ducks (Anas platyrhynchos)

Pharmacokinetics and pharmacodynamics of alfaxalone was performed in mallard ducks (Anas platyrhynchos) after single bolus injections of 10 mg/kg administered intramuscularly (IM; n = 10) or intravenously (IV; n = 10), in a randomized cross‐over design with a washout period between doses. Mean (±SD) C_max following IM injection was 1.6 (±0.8) µg/ml with T_max at 15.0 (±10.5) min. Area under the curve (AUC) was 84.66 and 104.58 min*mg/ml following IV and IM administration, respectively. Volume of distribution (V_D) after IV dose was 3.0 L/kg. The mean plasma clearance after 10 mg/kg IV was 139.5 (±67.9) ml min^?1 kg^?1. Elimination half‐lives (mean [±SD]) were 15.0 and 16.1 (±3.0) min following IV and IM administration, respectively. Mean bioavailability at 10 mg/kg IM was 108.6%. None of the ducks achieved a sufficient anesthetic depth for invasive procedures, such as surgery, to be performed. Heart and respiratory rates measured after administration remained stable, but many ducks were hyperexcitable during recovery. Based on sedation levels and duration, alfaxalone administered at dosages of 10 mg/kg IV or IM in mallard ducks does not induce clinically acceptable anesthesia.     

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,利用高效液相色谱法(high performance liquid chromatography, HPLC)测定血浆中FFC含量。结果显示,此试验所建立的HPLC色谱图基线平稳,血浆峰与FFC峰完全分离。回收率和精密度均符合测定要求,重复性好,适用于鸡血浆FFC含量测定。药动学参数结果显示,与FFC组相比,FFC-NC组的达峰时间t_max为(0.875±0.137) h,峰时缩短,药时曲线下面积AUC₍(0-∞))和峰浓度C_max分别为(23.957±2.338) mg/(L·h)和(8.249±0.713) mg/L,FFC-NC组的相对生物利用度是FFC组的3.6倍。结果表明,FFC-NC的药动学特征较FFC均...     

替米考星静脉及皮下注射后在绵羊体内的药代动力学研究

健康成年杂交绵羊静脉和皮下注射替米考星注射液后,用反相高效液相色谱法测定不同时间点血清中的药物浓度。采用3p97药代动力学程序软件处理数据,替米考星两种给药途径的药 时数据均符合二室开放模型静脉注射给药(5 mg/kg bw)的主要药代动力学参数: t1/2a 为 0. 611±0. 017 h、t1/2β为 23. 215±0. 459 h、AUC为11 815±0.396(μg/mL)·h、CL(s)为 0.424±0.014 L/(kg·h)。替米考星皮下注射主要药代动力学参数: 1mg/kg bw剂量组 t1/2a 为 1 751±0 557 h、t1/2β为 22 896±2 747 h、t1/2Ka 为 0. 100±0. 025 h、AUC 为 25. 828±1 479 (μg/mL)·h、CL(s)为0.393±0.017 L/(kg·h),Tmax为0.500±0.065 h,Cmax为1.424±0.156μg/mL、F为109.28%±6.25%。30 mg/kg bw剂量组 t1/2a为1.342±0.244 h、t1/2β为 20.052±1.236 h、t1/2Ka为 0.086±0.015h、AUC为57 575±6.760 (μg/mL)·h、CL(s)为0.527±0.068 L/(kg·h)、Tmax为0.437±0.039 h、Cmax为 3.343±0 512μg/mL、F为81.22%±9.54%。结果表明,绵羊静脉和皮下注射替米考星体内分布广,消除缓慢;皮下注射后在体内吸收迅速,达峰快,生物利用度高。     

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     

儿茶素在家兔体内的生物利用度及药物动力学研究

选健康家兔 ,单剂量静注和灌服儿茶素 (Catechin) 2 5 mg/ kg,用高效液相色谱法测定其血药浓度 ,3P87计算机程序处理所得血药浓度—时间数据。结果健康家兔静注给药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 .15± 0 .0 1) h,t1 /2β(0 .5 8± 0 .0 2 ) h,Vc (1.4 1± 0 .0 8) l,Vβ(2 .97± 0 .11) l,Cl B(3.5 3±0 .10 ) l/ h,AU C(16 .95± 1.5 2 ) mg/ (l· h) ,K1 0 (2 .5 2± 0 .2 0 ) h- 1 ,K2 1 (2 .2 5± 0 .15 ) h- 1 ,K1 2 (1.17± 0 .15 )h- 1 。健康家兔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 /2 ka(0 .39± 0 .0 6 )h,t1 /2 ke(0 .79± 0 .11) h,tmax(0 .78± 0 .11) h,Cmax(3.35± 0 .16 ) mg/ l,AU C (7.4 5± 0 .94 ) m g/ (l· h) ,F (6 4±7.0 0 ) %。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     

鸡组织中尼卡巴嗪残留HPLC检测方法的研究

建立了尼卡巴嗪标识残留物在鸡组织中残留的HPLC检测方法.样品用乙腈提取,正己烷脱脂,C18固相小柱净化.以乙腈:水(52: 48)为流动相,紫外检测器在波长340 nm处检测.在该检测条件下,尼卡巴嗪标示残留物DNC的检测限为31.25μg/kg,定量限为100μg/kg.DNC工作液在31.25～8 000 μg/kg范围内药物浓度与峰面积呈良好的线性关系(r=0.999 9).尼卡巴嗪在鸡肌肉、肝脏和肾脏中添加浓度分别为0.1、0.2和0.4 μg/g时,样品回收率在80.06%～89.87%之间.批内变异系数小于7.09%,批间变异系数小于6.34%.     

伊维菌素在不同动物中安全性、药效学和药代动力学的差异性研究进展

伊维菌素是一种被广泛应用于多种畜禽线虫病和外寄生虫病防控的抗寄生虫药物。由于伊维菌素具有非常突出的优点,在不同种属动物上使用时,其安全性、药效学和药代动力学的差异更容易被人们忽略。忽略动物种属差异,可能会导致寄生虫病防治失败,甚至安全事故的发生。对伊维菌素在不同动物中的安全性、药效学和药代动力学差异做一综述,以期为伊维菌素的临床用药提供参考,保障伊维菌素在不同动物中用药的安全性和有效性。     

三种抗菌药体外对鸡败血支原体的敏感性

本研究测定了蒽诺沙星、泰乐菌素及土霉素对鸡败血支原体（BG44T株）的体外最小抑菌浓度（MIC）及泰乐菌素与土霉素的联合药敏作用。MIC测定采用试管两倍稀释法，联合药敏采用棋盘法，重复三次试验，以平均值作为结果。蒽诺沙星、泰乐菌素及土霉素对鸡败血支原体的MIC分别为0.025μg/ml、0.00625μg/ml和0.5μg/ml。泰乐菌素与土霉素的联合药敏试验的抑菌浓度指数为0.5，合用有协同作用。