氟苯尼考及其代谢物氟苯尼考胺在鸡肌肉中的残留消除规律

本试验旨在研究氟苯尼考及其代谢物氟苯尼考胺在鸡肌肉中的残留消除规律。鸡肌肉样品经丙酮、二氯甲烷提取,饱和正己烷脱脂,氮吹仪吹干浓缩后,以乙腈-磷酸二氢钠溶液(0.01mol.L-1,含0.005mol.L-1十二烷基硫酸钠和0.1%三乙胺)(体积比35∶65)为流动相,流速为1.0mL.min-1,在激发波长225nm、发射波长285nm处用高效液相色谱荧光检测器检测。结果:测得鸡肌肉中氟苯尼考、氟苯尼考胺的检测限分别为1.5和0.5μg.kg-1(S/N=3)、定量限分别为5和2μg.kg-1(S/N=10)。各试验组京海黄鸡分别按体质量以25.0、50.0和100.0mg.kg-1.d-1剂量给药,每天1次,连续5d内服给药后,休药第1天时,鸡肌肉中氟苯尼考及其代谢物氟苯尼考胺的残留量均达到峰值,且残留量随给药剂量的增大而增大,随休药期的延长而降低。休药第7天时,鸡肌肉中氟苯尼考及其代谢产物氟苯尼考胺的总残留量均低于MRLs(100μg.kg-1);休药第11天时,鸡肌肉中氟苯尼考及其代谢产物氟苯尼考胺的总残留量均低于检测限;氟苯尼考、氟苯尼考胺在鸡肌肉中的残留量及其总残留量均与给药剂量呈正相关。     

Pharmacokinetics of florfenicol and its metabolite florfenicol amine in crucian carp (Carassius auratus) at three temperatures after one single intramuscular injection

The pharmacokinetic profiles of florfenicol (FF) or florfenicol amine (FFA) in crucian carp were compared at different water temperatures after single intramuscular administration of FF at 10 mg/kg bodyweight. The concentrations of FF and FFA were determined by a high‐performance liquid chromatography method, and then, the concentration versus time data were subjected to compartmental analysis using a one‐compartment open model. At the water temperatures of 10, 20, and 25°C, the peak concentrations (C_maxs) of FF were 2.28, 2.29, and 2.34 μg/ml, respectively, while those of FFA were 0.42, 0.71, and 0.82 μg/ml, respectively. And the absorption half‐life (t_1/2ka) of FF was 0.21, 0.19, and 0.21 hr, while the elimination half‐life (t_1/2kel) was 31.66, 24.77, and 21.48 hr, respectively. For FFA, the formation half‐life (t_1/2kf) was 3.85, 8.97, and 12.43 hr, while the t_1/2kel was 58.34, 30.27, and 21.22 hr, respectively. The results presented here demonstrated that the water temperature had effects on the elimination of both FF and FFA and the formation of FFA. Based on the T > MIC values calculated here, to treat the infections of bacterial with MIC value ≤ 0.5 μg/ml, FF intramuscularly given at 10 mg/kg bodyweight with a 72‐hr interval is sufficient at the water temperature of 10°C, while the intervals of 60 and 48 hr were needed at 20 and 25°C, respectively. But to treat bacterial with higher MIC values, more FF or FF at 10 mg/kg BW but with shorter intervals should be intramuscularly given to the infected fish.     

Pharmacokinetics of florfenicol and its metabolite,florfenicol amine,in rice field eel (Monopterus albus) after a single‐dose intramuscular or oral administration

The pharmacokinetics of florfenicol (FF) and its metabolite, florfenicol amine (FFA), were studied in rice field eel (Monopterus albus) after a single dose (20 mg/kg) by intramuscular (i.m.) or oral gavage (p.o.) dose at 25 °C. The elimination half‐lives (t_1/2β), peak concentration of FF (C_max), and time to reach FF peak concentration (T_max) in plasma were estimated as 18.39 h, 10.83 μg/mL, and 7.00 h, respectively, after i.m. injection and 13.46 h, 8.37 μg/mL, and 5 h, respectively, after p.o. administration. The T_max values of FF in tissues (i.e., kidney, muscle, and liver) were larger for i.m. injection compared with those for p.o. administration. The t_1/2β had the following order kidney > muscle > liver for i.m. administrated and kidney > liver > muscle for p.o. administrated. The largest area under the concentration–time curve (AUC) was calculated to be 384.29 mg · h/kg after i.m. dosing, and the mean residence time (MRT) was 42.46 h by oral administration in kidney. FFA was also found in all tissues with a lower concentration than FF for both i.m. and p.o. administrations throughout the study. The elimination of FFA was slow with a t_1/2β between 18.19 and 47.80 h in plasma and tissues. The mean metabolic rate of FFA for i.m. and p.o. administrations was >23.30%.     

Pharmacokinetics of florfenicol in blunt‐snout bream (Megalobrama amblycephala) at two water temperatures with single‐dose oral administration

The pharmacokinetics and residue elimination of florfenicol (FFC) and its metabolite florfenicol amine (FFA) were studied in healthy blunt‐snout bream (Megalobrama amblycephala, 50 ± 10 g). The study was conducted with a single‐dose (25 mg/kg) oral administration at a water temperature of 18 or 28°C, while in the residue elimination study, fish were administered at 25 mg/kg daily for three consecutive days by oral gavage to determine the withdrawal period (WDT) at 28°C. The FFC and FFA levels in plasma and tissues (liver, kidneys and muscle) were analysed using high‐performance liquid chromatography (HPLC). A no‐compartment model was used to analyse the concentration versus time data of M. amblycephala. In the two groups at 18 and 28°C, the maximum plasma concentration (C_max) of FFC was 5.89 and 6.21 μg/ml, while the time to reach C_max (T_max) was 5.97 and 2.84 hr, respectively. These suggested that higher temperature absorbed more drug and more quickly at M. amblycephala. And the elimination half‐life (T_1/2kβ) of FFC was calculated as 26.75 and 16.14 hr, while the total body clearance (CL) was 0.09 and 0.15 L kg^?1 hr^?1, and the areas under the concentration–time curves (AUCs) were 265.87 and 163.31 μg hr/ml, respectively. The difference demonstrated that the elimination rate of FFC in M. amblycephala at 28°C was more quickly than that at 18°C. The results of FFA showed the same trend in tissues of M. amblycephala. After multiple oral doses (25 mg/kg daily for 3 days), the k (eliminate rate constant) of FFA in M. amblycephala muscle was 0.017, the C₀ (initial concentration) was 3.07 mg/kg, and the WDT was 10 days (water temperature 28°C).     

Diffusion‐limited PBPK model for predicting pulmonary pharmacokinetics of florfenicol in pig

For most bacterial lung infections, the concentration of unbound antimicrobial agent in lung interstitial fluid has been thought to be responsible for antimicrobial efficacy. In this study, a diffusion‐limited physiologically based pharmacokinetic (PBPK) model was developed to predict the pulmonary pharmacokinetics of florfenicol (FF) in pigs. The model included separate compartments corresponding to blood, diffusion‐limited lung, flow‐limited muscle, liver, and kidney and an extra compartment representing the remaining carcass. The absorption rate constant and renal and hepatic clearance of FF were determined in vivo. Other parameters were taken from the literature or optimized based on existing pharmacokinetic data. All mathematical operations during the development of the model were performed using acslXtreme version 3.0.2.1 (Aegis Technologies Group, Inc., Huntsville, AL, USA). The model accurately predicted the concentration–time courses of FF in lung interstitial fluid, serum, and plasma following different dosing schedules, except at the dose of 15 mg/kg. When compared with the tissue residue data, the model generally underestimated the FF concentration at the injection site, whereas it gave good predictions of FF concentrations in lung, liver, and kidney at early time points. The model predictions provide a scientific basis for the dosage regimen design of FF.     

氟苯尼考注射液在鸡体内残留消除研究

［摘 要］为研究氟苯尼考注射液在鸡体内的残留消除规律。本实验采用35只约3kg左右的健康白羽鸡,随机分为2组,给药组30只,对照组5只。给药组用药量为20mg/kg/次,每隔48小时用药1次,连用2次,对照组不给任何抗菌药物,与给药组同环境饲养。在最后一次给药6h、24h(1天)、72h(3天)、120h(5天)、168h(7天)时采集肉、肝、肾、皮脂样本,经LC-MS/MS法测定组织中的氟苯尼考及其标示物氟苯尼考胺残留量,并利用WT1.4软件计算休药期。结果显示：氟苯尼考注射液在鸡肌肉、肝脏、肾脏及皮脂中的休药期分别是3.41d、2.06d、2.25d、1.47d。为保证兽药使用安全、消费者健康和食品安全,推荐氟苯尼考注射液在鸡体内的休药期为4d。     

高效液相色谱荧光检测法同时检测鸡肉中氟苯尼考及氟苯尼考胺残留

经丙酮、二氯甲烷提取,饱和正己烷脱脂,氮吹仪吹干浓缩后,以乙腈-磷酸二氢钠溶液(0.01 mol/L,含0.005mol/L十二烷基硫酸钠和0.1%三乙胺)(35 :65)为流动相,流速为1.0 mL/min,荧光检测激发波长为225 nm,发射波长285 nm.氟苯尼考在0.01～10.0 mg/L、氟苯尼考胺在0.002 5～2.5 mg/L浓度范围内,本方法线性关系良好,相关系数分别为0.999 7和0.999 8.当添加水平氟苯尼考为15～500 μg/kg、氟苯尼考胺为5～500μg/kg时.该方法平均回收率分别为79.5%～84.6%和80.7 0A～88.2%,相对标准偏差分别为2.8%～6.4%和2.4%～5.3%;检测限分别为5μg/kg和μg/kg.该方法样品处理简单,可同时检测氟苯尼考和氟苯尼考胺的残留,且准确度和精密度均符合残留分析的要求.     

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.     

A physiologically based pharmacokinetics model for florfenicol in crucian carp and oral‐to‐intramuscular extrapolation

Yang, F., Sun, N., Sun, Y. X., Shan, Q., Zhao, H. Y., Zeng, D. P., Zeng, Z. L. A physiologically based pharmacokinetics model for florfenicol in crucian carp and oral‐to‐intramuscular extrapolation. J. vet. Pharmacol. Therap.  36 , 192–200. In this study, an oral physiologically based pharmacokinetics (PBPK) model was developed for florfenicol in crucian carp (Carassius auratus). Subsequently, oral‐to‐intramuscular extrapolation was performed and the two models were used to predict florfenicol concentrations in the edible tissues of crucian carp. The oral model gave good predictions in most tissues, except for kidney and liver in which the florfenicol concentrations were underestimated at the later time points. In contrast, using the intramuscular model, the concentrations in the kidney were overestimated at the later time points. Both models had the best predictive ability in the main edible tissue, the muscle. The oral model also accurately predicted the florfenicol concentrations in the muscle after multiple doses. The present study demonstrated the feasibility of predicting florfenicol concentrations in the edible tissues of crucian carp using a route‐to‐route extrapolation method.     

Bath immersion pharmacokinetics of florfenicol in Nile tilapia (Oreochromis niloticus)

Drug administration by immersion can be a preferable method in certain conditions especially for treating small-sized, anorexic, or valuable fish. Pharmacokinetic information regarding bath treatment is considerably lacking in comparison to other common administration routes. The current study aimed to investigate if immersion can be an effective route to administer florfenicol (FF) for treatment in Nile tilapia. Nile tilapia reared at 28°C were immersed with FF solution at concentrations of 50, 100, 200, 500, and 500/200 (3 hr/117 hr) ppm for 120 hr and moved to drug-free freshwater for another 24 hr. The serum FF concentration in 100, 200, and 500/200 ppm groups reached steady-state at 12 hr with concentrations of 2.44, 3.04, and 5.26 µg/ml, respectively, which were about 2% of the bathing concentrations. The target therapeutic levels of 1–4 µg/ml were attained and maintained within 1–12 hr, depending on the immersion concentration and the target MIC. Serum FF reached the target with shorter time at higher bathing concentration. Following the 120-hr bath, the serum FF declined with the first-order half-life of approximately 10 hr. A minimum of 100 ppm FF is required for treatment purpose, and an initial high loading concentration followed by maintenance concentration is a plausible way to reach in vivo therapeutic level in short time. Greater than 99% of the residual FF in the bathing water could be removed within 15 min by 0.05% NaOCl. Our results indicated that bath immersion is a promising potential route for FF administration in Nile tilapia.     

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.     

Preparation,characterization, and pharmacokinetics in swine of a florfenicol enteric formulation prepared using hot‐melt extrusion technology

The objective of this work was to manufacture an enteric formulation of florfenicol (FF) using hot‐melt extrusion (HME) technology and to evaluate its in vitro dissolution and in vivo pharmacokinetics. For the HME process, hypromellose acetate succinate LG (HPMCAS‐LG) was the enteric polymer mixed with FF, and the two components were extruded with a standard screw configuration at a speed of 50 rpm. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X‐ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FT‐IR) were performed to characterize the HME extrudate. The release percentage of the enteric formulation in the acidic stage was <10% of the loaded FF, whereas that in the phosphate buffer stage was >80%. Pharmacokinetic evaluations in swine revealed that the enteric formulation had a longer t_1/2λ and MRT than commercially available FF powder (FULAIKA^®), indicating that the novel formulation exhibited enteric and sustained release properties. Compared with the commercial product, the relative bioavailability of the enteric formulation reached up to 117.2%. This study suggests that this formulation may have potential for future commercialization.     

水产品中甲砜霉素、氟苯尼考和氟苯尼考胺酶联免疫多残留测定

将氟苯尼考胺与载体蛋白相连作为抗原免疫动物,获得抗甲砜霉素等药物的抗体,建立了水产品中甲砜霉素、氟苯尼考和氟苯尼考胺残留的ELISA检测方法。结果显示,人工抗原中氟苯尼考胺与蛋白质分子的结合比约为12∶1,血清效价达到1∶2000倍以上,50%抑制浓度(IC50)为3μg/L左右,3种酰胺醇类药物交叉反应率在30%～156%之间,鱼和虾肌肉组织中的检测限分别为6.3μg/kg和6.1μg/kg,在鱼和虾肌肉组织中三种药物的回收率在40%～120%之间,检测范围为0.2～125μg/L。该方法可同时测定甲砜霉素、氟苯尼考及其标示残留物氟苯尼考胺等3种化合物残留量。方法灵敏度、精密度和准确度均能满足兽药残留筛选检测要求。     

Determination of sulfadiazine,trimethoprim, and N4‐acetyl‐sulfadiazine in fish muscle plus skin by Liquid Chromatography–Mass Spectrometry. Withdrawal‐time calculation after in‐feed administration in gilthead sea bream (Sparus aurata L.) fed two different diets

This study presents a depletion study for sulfadiazine and trimethoprim in muscle plus skin of gilthead sea bream (Sparus aurata L.). N⁴‐acetyl‐sulfadiazine, the main metabolite of sulfadiazine (SDZ), was also examined. The fish were held in seawater at a temperature of 24–26 °C. SDZ and trimethoprim (TMP) were administered orally with medicated feed for five consecutive days at daily doses of 25 mg SDZ and 5 mg TMP per kg of fish body weight per day. Two different diets, fish oil‐ and plant oil‐based diets, were investigated. Ten fish were sampled at each of the days 1, 3, 5, 6, 8, 9, 10, and 12 after the start of veterinary medicine administration. However for the calculation of the withdrawal periods, sampling day 1 was set as 24 h after the last dose of the treatment. Fish samples were analyzed for SDZ, TMP, and acetyl‐sulfadiazine (AcSDZ) residues by liquid chromatography–mass spectrometry. SDZ and TMP concentrations declined rapidly from muscle plus skin. Considering a maximum residue limit of 100 μg/kg for the total of sulfonamides and 50 μg/kg for TMP residues in fish muscle plus skin, the withdrawal periods of the premix trimethoprim‐sulfadiazine 50% were calculated as 5 and 6 days, at 24–26 °C, in fish oil (FO) and plant oil (PO) groups, respectively. The investigation of this work is important to protect consumers by controlling the undesirable residues in fish.     

Tilmicosin‐ and florfenicol‐loaded hydrogenated castor oil‐solid lipid nanoparticles to pigs: Combined antibacterial activities and pharmacokinetics

The combined antibacterial effects of tilmicosin (TIL) and florfenicol (FF) against Actinobacillus pleuropneumoniae (APP) (n = 2), Streptococcus suis (S. suis) (n = 2), and Haemophilus parasuis (HPS) (n = 2) were evaluated by chekerboard test and time‐kill assays. The pharmacokinetics (PKs) of TIL‐ and FF‐loaded hydrogenated castor oil (HCO)‐solid lipid nanoparticles (SLN) were performed in healthy pigs. The results indicated that TIL and FF showed synergistic or additive antibacterial activities against APP, S. suis and HPS with the fractional inhibitory concentration (FIC) ranging from 0.375 to 0.75. The time‐kill assays showed that 1/2 minimum inhibitory concentration (MIC) TIL combined with 1/2 MIC FF had a stronger ability to inhibit the growth of APP, S. suis, and HPS than 1 MIC TIL or 1 MIC FF, respectively. After oral administration, plasma TIL and FF concentrations could maintain about 0.1 μg/ml for 192 and 176 hr. The SLN prolonged the last time point with detectable concentrations (T_last), area under the concentration–time curve (AUC_0‐t), elimination half‐life (T_½ke), and mean residence time (MRT) by 3.1, 5.6, 12.7, 3.4‐fold of the active pharmaceutical ingredient (API) of TIL and 11.8, 16.5, 18.1, 12.1‐fold of the API of FF, respectively. This study suggests that the TIL‐FF‐SLN could be a useful oral formulation for the treatment of APP, S. suis, and HPS infection in pigs.     

加速溶剂萃取/超高效液相色谱-荧光法检测猪肉中氟苯尼考和氟苯尼考胺残留

为给动物源性食品中同时检测氟苯尼考（FF）及其主要代谢产物氟苯尼考胺（FFA）的残留提供新的安全可靠的方法，本研究建立了猪肉中FF及FFA残留检测的加速溶剂萃取/超高效液相色谱-荧光检测（ASE/UPLC-FLD）法。试验采用乙酸乙酯：氨水（98：2，V/V）为提取剂，样品经加速溶剂萃取后浓缩，用乙酸乙酯饱和正己烷除脂，再经浓缩复溶后进行UPLC-FLD检测。结果表明，FF及其代谢产物FFA在添加浓度为9.8~400和3.2~400 μg/kg的范围内线性关系良好，相关系数（R²）分别为0.9993和0.9999。FF的检测限（LOD）和定量限（LOQ）分别为3.3和9.8 μg/kg；FFA的LOD和LOQ分别为1.2和3.2 μg/kg。样品在LOQ、0.5 MRL、1.0 MRL和2.0 MRL加标水平下的平均回收率为82.92%~96.72%，相对标准偏差（RSD）低于3.11%。综上所述，加速溶剂萃取（ASE）方法省时、环保、提取效率高，超高效液相色谱-荧光检测（UPLC-FLD）检测方法高效、灵敏、回收率高，是符合检测标准的新方法。     

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.     

Comparative pharmacokinetics of florfenicol in healthy and Pasteurella multocida‐infected Gaoyou ducks

Pasteurella multocida is the causative agent of fowl cholera, and florfenicol (FF) has potent antibacterial activity against P. multocida and is widely used in the poultry industry. In this study, we established a P. multocida infection model in ducks and studied the pharmacokinetics of FF in serum and lung tissues after oral administration of 30 mg/kg bodyweight. The maximum concentrations reached (C_max) were lower in infected ducks (13.88 ± 2.70 μg/ml) vs. healthy control animals (17.86 ± 1.57 μg/ml). In contrast, the mean residence time (MRT: 2.35 ± 0.13 vs. 2.27 ± 0.18 hr) and elimination half‐life (T_½β: 1.63 ± 0.08 vs. 1.57 ± 0.12 hr) were similar for healthy and diseased animals, respectively. As a result, the area under the concentration curve for 0–12 hr (AUC_0–12 hr) for FF in healthy ducks was significantly greater than that in infected ducks (49.47 ± 5.31 vs. 34.52 ± 8.29 μg hr/ml). The pharmacokinetic differences of FF in lung tissues between the two groups correlated with the serum pharmacokinetic differences. The C_max and AUC_0–12 hr values of lung tissue in healthy ducks were higher than those in diseased ducks. The concentration of FF in lung tissues was approximately 1.2‐fold higher than that in serum both in infected and healthy ducks indicating that FF is effective in treating respiratory tract infections in ducks.     

Total radioactive residues and clenbuterol residues in swine after dietary administration of [14C]clenbuterol for seven days and preslaughter withdrawal periods of zero, three, or seven days

Nine barrows (23.8 +/- 0.9 kg) and 9 gilts (23.1 +/- 0.9 kg) were used to determine the disposition of radiocarbon after oral [14C]clenbuterol (4-amino-alpha-[t-butylaminomethyl]-3,5-dichlorobenzyl [7-(14)C]alcohol hydrochloride) administration and to determine total and parent residues in edible tissues. Three barrows and three gilts, housed in metabolism crates, were fed 1 ppm [14C]clenbuterol HCl for seven consecutive days in three separate trials; a single barrow and gilt from each trial was slaughtered after 0-, 3-, or 7-d preslaughter withdrawal periods. Urine and feces were collected during the dosing and the withdrawal period; edible and inedible tissues were collected at slaughter. Total recovery of radiocarbon was 94.2 +/- 6.5%. Total clenbuterol absorption was greater than 75% for barrows and 60% for gilts. Total radioactive residues in tissues were not different (P > 0.05) between barrows and gilts. Concentrations of parent clenbuterol in liver, kidney, skeletal muscle, adipose tissue, and lung did not differ between barrows and gilts (P > 0.05). Total radioactive and parent residues declined in tissues as withdrawal period increased. After the 0-d withdrawal period, total liver residues (286 ppb) were approximately equal to lung residues, twice those of the kidney, and about 15 times those of adipose tissue and skeletal muscle. After a 7-d withdrawal period, total radioactive residues in liver (15 ppb) were roughly three times greater than lung, kidney, and adipose tissue total residues and about 13 times those of skeletal muscle total residues. Parent clenbuterol represented 79, 63, 42, 67, and 100% of the total radioactive residue in adipose tissue, kidney, liver, lung, and skeletal muscle, respectively, in hogs slaughtered with a 0-d withdrawal period. With increasing withdrawal period, the percentage of total radioactive residue present as parent clenbuterol within edible tissues (including lung) decreased, so that after a 7-d withdrawal period, 7, 16, and 29% of the total residue was composed of parent clenbuterol in kidney, liver, and lung, respectively. After a 7-d withdrawal period, parent clenbuterol exceeded the European maximum residue limit (0.5 ppb) 4.6-fold in liver and 2.4-fold in lung. In muscle, clenbuterol was approximately 40 times the limit after a 0-d withdrawal period but had dropped below 0.5 ppb after a 3-d withdrawal period. Results from this study indicate that clenbuterol HCl is well absorbed in swine and that the use of clenbuterol in this species in an off-label manner is inconsistent with human food safety standards used in developed countries.     

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.