Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin in Male and Female Turkeys following Intravenous and Oral Administration

The pharmacokinetics of enrofloxacin (EFL) was investigated in turkeys (6 male and 6 female; 7-month-old at the start of the experiment), after intravenous and oral administration at a dose of 10 mg/kg body weight. The serum concentrations of EFL and its active metabolite ciprofloxacin (CFL) were determined by high-performance liquid chromatography. The serum concentrations vs time were analysed by a compartmental analysis. The mean values of EFL pharmacokinetic parameters showed differences only between values of V_d,ss (3.46±0.19 for the females and 4.53±0.11 L/kg for the males, p>0.05). The metabolite CFL was eliminated more slowly than its parent compound. There were no statistically significant differences between the values of the CFL pharmacokinetic parameters calculated for both sexes, excluding the higher values (p>0.05) of C_max in the females. The ratio AUC_CFL/AUC_EFL×100 was 4.4% in the male and 6.84% in the female birds. After oral administration of EFL the values of F(%) were 77.83 in the female and 79.61 in the male turkeys. Higher CFL serum concentrations were measured in females (p>0.05). The pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in turkeys can be characterized as similar to that in chickens and very similar between both sexes.     

Pharmacokinetics of Pefloxacin in Goats after Intravenous or Oral Administration

The plasma concentrations and pharmacokinetics of the fluoroquinolone antimicrobial agent pefloxacin, following the administration of a single intravenous (10 mg/kg) or oral (20 mg/kg) dose, were investigated in healthy female goats. The antimicrobial activity in plasma was measured at predetermined times after drug administration by an agar well diffusion microbiological assay, using Escherichia coli (ATCC 25922) as the test organism. Concentrations of the drug 0.25 g/ml were maintained in plasma for up to 6 and 10 h after intravenous (IV) or oral administration of pefloxacin, respectively. The concentration–time data for pefloxacin in plasma after IV or oral administration conformed to two- and one-compartment open models, respectively. Plasma pefloxacin concentrations decreased rapidly during the initial phase after IV injection, with a distribution half-life (t _1/2 ) of 0.10±0.01 h. The terminal phase had a half-life (t _1/2 ) of 1.12±0.21 h. The volume of distribution at steady state (V _dss), mean residence time (MRT) and total systemic clearance (Cl_B) of pefloxacin were 1.08±0.09 L/kg, 1.39±0.23 h and 821±88 (ml/h)/kg, respectively. Following oral administration of pefloxacin, the maximum concentration in the plasma (C _max) was 2.22±0.48 g/ml and the interval from administration until maximum concentration (t _max) was 2.3±0.7 h. The absorption half-life (t _{1/2 ka}), mean absorption time (MAT) and elimination half-life of pefloxacin were 0.82±0.40, 4.2±1.0 and 2.91±0.50 h, respectively. The oral bioavailability of pefloxacin was 42%±5.8%. On the basis of the pharmacokinetic data, a dosage regimen of 20 mg/kg, IV at 8 h intervals or orally twice daily, is suggested for treating infections caused by drug-sensitive pathogens in goats.     

Pharmacokinetics and Dosage Regimen of Enrofloxacin in Buffalo Bulls after Intramuscular Administration

The disposition kinetics and dosage regimen of enrofloxacin were investigated in breeding buffalo bulls following a single intramuscular administration of 5 mg/kg. The absorption half-life, half-life of the terminal phase, apparent volume of distribution and total body clearance were 0.262±0.099 h, 1.97±0.23 h, 0.61±0.13 L/kg and 210.2±18.6 ml/(kg.h), respectively. Therapeutic plasma levels (1 g/ml) were maintained for up to 6 h. A satisfactory intramuscular dosage regimen for enrofloxacin in buffalo bulls would be 8.5 mg/kg followed by 8.0 mg/kg at 8 h intervals.     

恩诺沙星及其活性代谢物在鸡体内的药物动力学

为全面了解恩诺沙星在鸡体内的动力学过程与药效的关系进行了本研究。用反向高效液相色谱法测定鸡血浆中的药物质量浓度,所得恩诺沙星ｃｉ－ｔｉ数据用ＭＣＰＫＰ计算机程序处理,代谢物环丙沙星的ｃｉ－ｔｉ数据用代谢物动力学方法处理。静注恩诺沙星后的ｃｉ－ｔｉ数据符合二室开放模型,主要动力学参数：ｔ１／２α（０．２５±０．０４）ｈ,ｔ１／２β（５．２６±０．８１）ｈ,Ｖｄ（４．５３±１．０７）Ｌ／ｋｇ,ＣＬＢ（０．６１±０．１１）Ｌ／（ｋｇ·ｈ）,ＡＵＣ（１７．３９±３．９２）ｍｇ／（Ｌ·ｈ）。内服恩诺沙星的ｃｉ－ｔｉ数据,符合有吸收因素二室模型,主要动力学参数ｔ１／２ｋａ（０．４４±０．１１）ｈ,ｔ１／２α（１．１５±０．３８）ｈ,ｔ１／２β（９．１４±１．４５）ｈ,ＡＵＣ（１２．４８±２．３６）ｍｇ／（Ｌ·ｈ）,ｔｍａｘ（１．７７±０．２１）ｈ,Ｃｍａｘ（１．４４±０．３１）ｍｇ／Ｌ,Ｆ７２．１８％。试验结果表明,鸡静注与内服恩诺沙星后,代谢物环丙沙星的生成及消除缓慢、分布广泛,是影响恩诺沙星疗效的重要因素。     

The Plasma Kinetics and Tissue Distribution of Enrofloxacin and its Metabolite Ciprofloxacin in the Muscovy Duck

Intorre, L., Mengozzi, G., Bertini, S., Bagliacca, M., Luchetti, E. and Soldani, G., 1997. The plasma kinetics and tissue distribution of enrofloxacin and its metabolite ciprofloxacin in the Muscovy duck. Veterinary Research Communications, 21 (2), 127-136The disposition and tissue distribution of enrofloxacin and of its main metabolite ciprofloxacin were investigated in ducks after oral or intramuscular administration of a single dose of 10 mg/kg enrofloxacin. Plasma and tissue concentrations were determined by a HPLC method. The peak concentrations of enrofloxacin after intramuscular administration (1.67 µg/ml at 0.9 h) were higher than after an oral dose (0.99 µg/ml at 1.38 h). The relative bioavailability of enrofloxacin after administration directly into the crop was 68%, while the metabolic conversion of enrofloxacin to ciprofloxacin was quite low (<10%) with both routes of administration. High tissue concentrations and high tissue:plasma concentration ratios were demonstrated for enrofloxacin and ciprofloxacin 24 h after treatment. It was concluded that a dose of 10 mg/kg per day provides serum and tissue concentrations sufficiently high to be effective in the control of many infectious diseases of ducks.     

Pharmacokinetic Disposition of Subcutaneously Administered Enrofloxacin in Goats

The pharmacokinetic disposition of enrofloxacin was studied in goats after subcutaneous (s.c.) administration at a single dose of 7.5 mg/kg body weight. Blood samples were drawn from a jugular vein into heparinized tubes at predetermined time intervals after administration of the drug and the plasma was separated by centrifugation. The concentrations of enrofloxacin in the plasma were determined by a microbiological assay using Escherichia coli as the test organism. The plasma concentration–time data were analysed by non-compartmental methods. Enrofloxacin was rapidly absorbed, an appreciable concentration of the drug (0.30±0.13 g/ml) being present in the plasma by 5 min after s.c. administration. The maximum plasma concentration of enrofloxacin and the time to reach that maximum were 2.91±0.39 g/ml and 2.9±0.51 h, respectively. A detectable concentration of enrofloxacin persisted in the plasma for 12 h. The elimination half-life and mean residence time of enrofloxacin were 2.84±0.57 and 5.74±0.28 h, respectively. It is suggested that enrofloxacin given subcutaneously may be useful in the treatment of susceptible bacterial infections in goats.     

恩诺沙星及其活性代谢物在传染性鼻炎鸡体的药动学

为建立鸡传染性鼻炎的药动学模型,研究了恩诺沙星及其活性代谢物在传染性鼻炎鸡体内的药动学特征.用反向高效液相色谱法测定血浆中的药物浓度,所得恩诺沙星的ci-ti数据用MCPKP程序处理,代谢物环丙沙星的ci-ti数据用代谢物动力学方法处理.结果表明,鸡静注恩诺沙星后的ci-ti数据符合二室开放模型,其主要动力学参数如下:t1/2α(0.25±0.04) h、t1/2β(5.46±0.71) h、Vd(4.21±1.09) L/kg、CLB(0.54±0.11) L/(kg.h)、AUC(19.68±3.50) mg/(L.h).鸡内服恩诺沙星的ci-ti数据,符合有吸收因素二室模型,其主要动力学参数如下:t1/2ka(0.44±0.11) h、t1/2α(1.17±0.40) h、t1/2β(9.24±2.07) h、AUC(12.23±3.68) mg/(L.h)、tmax(1.50±0.29) h、Cmax(1.34±0.44) mg/L、F 62.26%.恩诺沙星在感染鸡体内的动力学特征是吸收迅速、分布广泛、消除缓慢;感染鸡静注与内服恩诺沙星后,代谢物环丙沙星的动力学特征是生成及消除缓慢、分布广泛.鸡传染性鼻炎可使恩诺沙星内服的生物利用度下降,但对恩诺沙星的分布、消除及代谢物的动力学过程无显著影响.     

环丙沙星在内毒素诱导的乳房炎奶山羊药动学及乳汁和组织浓度

将 1 5头健康杂交奶山羊均分成 3组 ,按每千克体重 5mg的剂量分别对大肠杆菌内毒素诱导的乳房炎奶山羊进行静注、肌注和乳房灌注单剂量环丙沙星药动学试验。高效液相色谱法测定血、乳及组织药物浓度 ,血药浓度 -时间数据用 MCPKP药动学程序处理。诱导乳房炎的奶山羊静注给药的药时数据符合二室开放模型 ,主要药动学参数分别为 :t1 /2α为 ( 0 .0 9± 0 .0 1 ) h,t1 /2β为 ( 1 .1 0± 0 .0 9) h,Vd( area) 为 ( 2 .80± 0 .3 0 ) L/kg,Cl B为 ( 1 .3 1± 0 .2 1 ) L/ ( kg·h- 1 ) ,AUC为 ( 3 .88± 0 .58) mg/ ( L· h- 1 )。肌注给药的药时数据符合一级吸收二室开放模型 ,主要药动学参数分别为 :t1 /2 Kα为 ( 0 .0 7± 0 .0 2 ) h,t1 /2α为 ( 0 .3 9± 0 .2 6) h,t1 /2β为 ( 2 .0 7±0 .4 3 ) h,tmax为 ( 0 .2 6± 0 .0 7) h,Cmax为 ( 1 .0 4± 0 .1 3 ) mg/ L,AUC为 ( 2 .3 8± 0 .1 3 ) mg/ ( L· h- 1 ) ,F为61 .3 4 %。与从健康奶山羊获得的药动学参数相比 ,急性乳房炎能显著影响环丙沙星静注给药的体内分布、转运和消除 ,对肌注给药无明显影响 ,乳房灌注给药在炎症乳房内的吸收个体差异较大。急性乳房炎能显著降低环丙沙星全身给药在乳内积聚程度。肌注后炎症乳腺组织内药物浓度在 2、4、6、8     

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。     

猪肌肉注射两种恩诺沙星注射液的药物动力学比较

选用6头健康杂种猪,随机交叉设计试验,进行肌注两种不同pH的恩诺沙星注射液(2.5 mg/kg)的药物动力学比较的研究.反相高效液相色谱法测定血浆中恩诺沙星的浓度.所得血药浓度-时间数据用MCPKP计算机程序处理.pH10.3及pH8.3的恩诺沙星注射液肌注给药的药时数据适合-级吸收一室模型,主要药物动力学参数分别是t1/2ka0.25±0.28 h及0.14±0.05 h;t1/2ke4.54±0.63及4.64±0.84 h;tmax0.95±0.70 h及0.69±0.23 h;Cmax0.96±0.16及0.92±0.29;AUC 7.58±1.10μg/ml·h及6.59±1.50μg/ml·h.两者的药物动力学参数无显著性差异(P＞0.05).     

恩诺沙星在猪体内的生物利用度及药物动力学研究

选用２１头健康杂种猪，随机分为３组，对静注、肌注及内服恩诺沙星（２．５ｍｇ／ｋｇ）的生物利用度和药物动力学进行了研究。用乙腈提取血浆中的药物，反相高效液相色谱法测定血浆中恩诺沙星及其主要代谢产物环丙沙星的浓度。所得血药浓药－时间数据用ＭＣＰＫＰ计算机程序处理。静注给药的药时数据适合二室开放模型，主要药物动力学参数：ｔ１／２ａ０．４８±０．２４ｈ；ｔ１／２ａ３．４５±０．８５ｈ；ｔ１／２Ｋ１０２．０     

环丙沙星在猪体内的生物利用度及药物动力学

18 头健康长白×大白×杜洛克杂交猪,分3 组,每组6 头,按5 m g/kg 的剂量进行了静注、肌注及内服环丙沙星的药动学研究。高效液相色谱法测定血浆中药物的质量浓度,MCPKP药代动力学程序处理药时数据。静注给药时,环丙沙星体内分布快且广泛,消除较慢,t1/2α为(0.35±0.19) h,t1/2β为(3.15±0.57) h,Vd(area)为(3.24±0.51) L/kg,ClB 为(0.73±0.15) L/(kg·h- 1 )。肌注和内服给药时,环丙沙星均吸收较快,但内服吸收速度和程度均不及肌注给药,t1/2ka 分别为(0.23±0.15)、(0.38±0 .21) h,tm ax 分别为(0.63±0.31)、(1.39±0.39) h,Cm ax 分别为(1.31±0.34)、(0.60±0.14) m g/L,生物利用度(F)分别为(77.96±5.89)% 、(51.58±5.69)% 。本研究发现,环丙沙星肌注和内服给药的消除半衰期与静注给药相似,分别为(3.45±0.66)、(3.32±0.96) h,与在其他哺乳动物的动力学特征有所不同。     

猪排泄物中恩诺沙星和环丙沙星含量的HPLC检测方法

为了对猪排泄物中恩诺沙星(enrofloxacin,ENR)和环丙沙星(ciprofloxacin,CIP)进行定量检测,试验建立了测定猪粪尿中ENR和CIP含量的高效液相－荧光检测方法。将猪粪经乙腈－氨水超声提取后,加入三氯乙酸酸化,然后分别将经磷酸酸化后的猪尿和提取后的猪粪溶液经固相萃取小柱富集净化,取净化液进行HPLC分析。HPLC流动相为乙腈(A):柠檬酸/乙酸铵缓冲液(B),梯度洗脱:0~25 min,A 10%~40%;25~30 min,A 40%至10%,荧光检测器的激发波长278 nm,发射波长465 nm。结果表明,ENR和CIP 在尿中的最低检测限(LOD)<0.01 mg/L,在粪中的LOD<0.021 mg/kg,在尿中的最低检测限(LOQ)<0.03 mg/L,在粪中LOQ<0.056 mg/kg,猪尿中的ENR和CIP在0.01~1.0 mg/mL范围内线性关系良好,R²分别为0.9994和0.9992;猪粪中的ENR和CIP在0.02~2.0 mg/mL范围内线性关系良好,R²分别为0.9986和0.9981。ENR在猪粪和猪尿中的回收率分别为79.4%和88.5%,CIP在猪粪和猪尿中的回收率分别为75.8%和89.9%。该方法样品处理简单,检测结果准确可靠,且灵敏度较高,是值得推广的检测方法。     

恩诺沙星微囊在猪体内的药动学及生物利用度研究

为了比较恩诺沙星微囊和原粉在猪体内的药动学特征及生物利用度,试验采用高效液相色谱法(HPLC),将10头健康猪分2组采用正交试验,经灌胃给药后采血、甲醇提取和HPLC分析,所得药时数据用MCPKP计算机程序处理。恩诺沙星微囊和原粉经口服给药后在猪体内的药时数据均符合一级吸收一室模型,主要药动学参数分别为:t1/2Ka1.73 h±0.93 h和0.36 h±0.31 h(P0.01);Tmax5.69 h±1.68 h和2.04 h±1.06 h(P0.01);t1/2Ke16.53 h±5.23 h和10.17 h±1.87 h(P0.01);Cmax1.71μg/mL±0.47μg/mL和2.51μg/mL±0.45μg/mL(P0.01);AUC为每小时51.98μg/mL±16.08μg/mL和40.58μg/mL±6.40μg/mL;微囊的相对生物利用度为128%。说明恩诺沙星微囊口服给药吸收较慢但完全,达峰时间较长,消除缓慢。     

Method for Determination of Enrofloxacin and Ciprofloxacin in Pig Excreta by HPLC

A HPLC-FLD method was developed for determination of enrofloxacin (ENR) and ciprofloxacin (CIP) levels in feces and urine of pig.The pig feces was ultrasonic extracted by acetonitrile-ammonia, then added trichloroacetic acid to make the extraction acidification.The pig urine was acidulated by phosphoric acid and the extraction of feces solution were enriched and purified by solid phase extraction small column, took purification liquid for HPLC analysis.Conditions of HPLC mobile phase was acetonitrile (A):citric acid/ammonium acetate buffer (B), the procedure of gradient elution was 0 to 25 min, A:10% to 40%;25 to 30 min, A:40% to 10%.The detector of fluorescence excitation wavelength was 278 nm, emission wavelength was 465 nm, chromatographic data were measured and recorded.The results showed that the LOD of ENR and CIP were lower than 0.01 mg/L in urine and 0.021 mg/kg in feces, the LOQ of ENR and CIP were lower than 0.03 mg/L in urine and 0.056 mg/kg in feces.ENR and CIP in the concentration of 0.01 to 1.0 mg/mL levels range had good linear relationship, R² were 0.9994 and 0.9992 in pig urine, respectively;ENR and CIP in the concentration of 0.02 to 2.0 mg/mL levels range had good linear relationship, R² were 0.9986 and 0.9981 in pig feces, respectively.The recovery ratio of ENR were 79.4% and 88.5%, and the recovery ratio of CIP were 75.8% and 89.9% in pig feces and urine.After get on validation, the method was easy in sample processing and testing, the results were accurate, reliable and high sensitivity, which was a worth promoting detection method.     

恩诺沙星和环丙沙星对金葡菌的抗菌后效应及抗菌后亚抑菌浓度效应

报告了抗菌后效应 (postantibiotic effect,PAE)、抗菌后亚抑菌浓度效应 (postantibiotic sub- MIC effect,PASME)、亚抑菌浓度效应 (sub- MIC effect,SME)研究的方法学和恩诺沙星、环丙沙星对金葡菌抗菌后效应及抗菌后亚抑菌浓度效应的研究结果。试验表明 :2、4MIC的恩诺沙星对金葡菌的 PAE为 1.0 3、1.5 0 h,1/2、1、2、4MIC的环丙沙星的 PAE为 0 .5 1、0 .88、1.47、1.92 h;1/8、1/4、1/2 MIC的恩诺沙星对经 4MIC药物诱导 1h的金葡菌可产生0 .38、1.15、>12 .31h的 PASME,1/8、1/4、1/2 MIC的环丙沙星的 PASME为 2 .6 9、>10 .17、>13.17h;1/8、1/4、1/2 MIC的恩诺沙星和环丙沙星对金葡菌产生的 SME分别为 0 .40、0 .91、>9.44 h和 0 .42、1.14、>9.0 2 h。上述结果说明 ,PAE、PASME和 SME的大小与药物浓度呈正相关 ,且环丙沙星比恩诺沙星对金葡菌有更长的效应     

Aspects of the Pharmacokinetics of Doxycycline Given to Healthy and Pneumonic East African Dwarf Goats by Intramuscular Injection

Ole-Mapenay, I.M., Mitema, E.S. and Maitho, T.E., 1997. Aspects of the pharmacokinetics of doxycycline given to healthy and pneumonic East African dwarf goats by intramuscular injection. Veterinary Research Communications, 21 (6), 453-462The effect of experimentally induced Pasteurella haemolytica pneumonia on the pharmacokinetics of doxycycline (Doxycen Retard) administered intramuscularly was studied in seven East African dwarf goats. The study was conducted in two consecutive phases, separated by a washout period of four weeks. The experimental infection, induced by intratracheal administration of 5 ml of 107 to 109 cfu/ml of Pasteurella haemolytica, produced a temperature rise, depression and laboured breathing within 6-12 days after inoculation.The concentrations of doxycycline in the serum were determined by a quantitative microbiological assay using an agar-gel diffusion method employing Bacillus cereus var mycoides (ATCC 11778) as the test organism, with a level of detectability of approximately 0.05 µg/ml. The concentration-time curve of doxycycline in the serum after intramuscular injection of 20 mg/kg bodyweight of the long-acting formulation before and after experimental infection was adequately described by a one-compartment open model.The maximum serum concentrations (Cmax) of doxycycline were lower in pneumonic goats than in healthy goats (3.87 ± 0.52 and 5.56 ± 0.213 µg/ml, respectively), suggesting an increased distribution volume in the peripheral compartment. The mean ± SEM absorption rate (ka) before infection (1.13 ± 0.02 h-1) was smaller than that after infection (8.23 ± 3.81 h-1), but the difference was not significant. The apparent elimination half-life (t1/2) (24.51 ± 0.02 h) after infection was significantly increased (p < 0.05), while the corresponding rate constant () was decreased (p < 0.01). The absorption half-life (t1/2) (0.137 ± 0.03 h) was significantly decreased (p < 0.01) after infection. The distribution volume (Vd()) was significantly increased after infection (p < 0.05). It is concluded that, although experimental infection had an effect on the disposition kinetics of doxycycline, this was not sufficiently pronounced to require alteration of the dosage during disease.     

恩诺沙星长效注射液肌注后在猪体内的药动学研究

研究了恩诺沙星长效注射液给猪肌注后的药物动力学特征。将12只白猪随机分成两组,每组6只,分别肌注恩诺沙星注射液(5mg/kg)和长效恩诺沙星注射液(18.75mg/kg),并于给药后0.1, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 60h, 从前腔静脉采取5ml血,用HPLC分析各血浆样品中的药物浓度,用MCPKP软件计算药动学参数。结果表明:长效恩诺沙星注射液肌注后,经5.64h达到4.86μg/ml的最高浓度,吸收半衰期和消除半衰期分别为2.42h和19.47h,有效浓度维持时间为128.73h, AUC为166.96mg/L.h。吸收半衰期显著延长(p<0.05),达峰时间极显著推迟(p<0.01),消除半衰期也显著长于恩诺沙星注射液。