Elimination Of Enrofloxacin Research Articles

Dynamic impacts of short-term bath administration of enrofloxacin on juvenile black seabream Acanthopagrus schlegelii

Dynamic impacts of short-term enrofloxacin (ENR) exposure on juvenile marine fish are not well understood, and the underlying mechanisms remain unclear. We therefore investigated the accumulation and elimination of ENR in the liver of juvenile black seabream Acanthopagrus schlegelii. Meanwhile, the dynamic alterations of biochemical parameters and liver transcriptomes after short-term bath immersion and withdrawal treatment were explored. The results indicated that the contents of ENR in the liver were significantly increased after bath administration for 24 h, and then quickly declined to very low concentrations along with the decontamination time increasing. Judging from the changes in biochemical indicators and liver transcriptomic alterations, 0.5 and 1 mg/L ENR exposure for 24 h triggered oxidative stress, impairment of immune system, as well as aberrant lipid metabolism via differential molecular pathways. Interestingly, biochemical and transcriptome analysis as well as integrated biomarker response (IBR) values showed that more significant changes appeared in 1 mg/L ENR group at decontamination periods, which indicated that the impact of high dose ENR on juvenile A. schlegelii may persist even after depuration for 7 days. These results revealed that the risk of short-term bath of 1 mg/L ENR should not be overlooked even after depuration period. Therefore, attention should be paid to the dosage control when administering the drug to juvenile A. schlegelii, and the restoration of physiological disturbance may be an important factor in formulating a reasonable treatment plan.

Pharmacokinetics, withdrawal period and risk assessment of enrofloxacin in the northern snakehead (Channa argus) following bath administration.

Enrofloxacin (ENR) is widely used in aquaculture practice, but little is known about its pharmacokinetic, withdrawal period and dietary risk in fish via bath administration. The purpose of this study was to provide data support for the use of ENR bath therapy in the northern snakehead (Channa argus). The pilot study was carried out to evaluate the therapy concentrations of ENR in northern snakehead with immersion concentrations ranged from 5 to 40 mg/L for 6 h. Based on results of the pilot study, an ENR immersion concentration of 20 mg/L was used for the formal experiment. At this dose, the peak concentrations of ENR in plasma, muscle plus skin, liver and kidney were 4.85, 4.55, 3.87 and 7.42 μg/mL (or g), respectively. According to the AUC0-∞ values, the distribution of ENR in northern snakehead followed the order of kidney > plasma > liver > muscle + skin. The elimination of ENR in northern snakehead was very slow, the half-lives (T1/2λz ) were up to 90.31, 85.5, 104.56 and 120.9 h in plasma, muscle plus skin, liver and kidney, respectively. Ciprofloxacin (CIP) was not detected in any samples in the pilot study and was only occasionally detected in muscle plus skin and liver samples in formal experiment. Based on the calculated PK/PD index AUC/MIC and Cmax /MIC, the current bath treatment regimen will have a good therapeutic effect on infections caused by bacteria with MIC below 0.6 μg/mL. The dietary risk assessment suggested that there was a dietary risk (Hazard Quotients > 10%) until day 6 after bath treatment. It is mandatory for ENR to maintain a withdrawal period of at least 450°C-day in northern snakehead after bath treatment ceased.

Pharmacokinetics and Tissue Residue Profiles of Enrofloxacin in Crucian Carp (Carassius auratus gibelio) Following Single and Multiple Oral Administration.

The pharmacokinetics, tissue distribution, and elimination of enrofloxacin (ENR) and its metabolite ciprofloxacin (CIP) were investigated to the crucian carp (Carassius auratus gibelio) after single (20 mg/kg b. w.) and multiple oral administration (20 mg/kg b.w. one time daily for 5 days) at 28°C. The concentrations of ENR and CIP in the plasma and tested tissues (muscle/skin, liver, and kidney) were detected simultaneously by high-performance liquid chromatography (HPLC), and the pharmacokinetic data were analyzed with a non-compartmental model using WinNonLin 6.1 PK software (Pharsight Corporation, Mountain View, CA, USA). The pharmacokinetic characteristics of ENR in crucian carp exhibited slow absorption, wide tissue distribution, and long elimination half-life. In the single-dose group, the peak concentrations (Cmax) of ENR in the plasma, muscle/skin, liver, and kidney were 8.93 μg/mL, 13.9 μg/g, 31.2 μg/g, and 27.3 μg/g, respectively, observed at 3 h, 6 h, 1 h, and 3 h after dosing. The elimination half-lives (T1/2λz) of ENR in plasma, muscle/skin, liver, and kidney were calculated to be 67.4, 82.8, 94.4, and 114 h, respectively. In the multiple-dose group, the Cmax of ENR in the plasma, muscle/skin, liver, and kidney were 18.4 μg/mL, 26.8 μg/g, 82.8 μg/g, and 74.5 μg/g, respectively, achieved at 3 h, 6 h, 1 h, and 1 h after the last dose. The T1/2λz of ENR in the plasma, muscle/skin, liver, and kidney were calculated to be 76.4 h, 91.5 h, 114 h, and 148 h, respectively. During the multiple-dose administration, significant accumulations of ENR and CIP were observed in the plasma and tissues of crucian carp, possibly due to their long elimination half-lives. In both dose groups, the AUC0−∞ for both ENR and CIP followed the order of liver > kidney > muscle/skin > plasma. The finding suggested that the liver may play an important role in the metabolism of ENR. According to the calculated PK/PD indices of Cmax/minimum inhibitory concentrations (MIC) and AUC24h/MIC, the multiple-dose regimen would be highly effective against pathogenic bacteria with a MIC value of ≤ 1.84 μg/ml. Depletion studies indicated that a withdrawal period of at least 29 or 32 days was necessary to guarantee food security after single or multiple oral gavage administration at 28°C.

Dynamic Elimination of Enrofloxacin Under Varying Temperature and pH in Aquaculture Water: An Orthogonal Study

Orthogonal experiments were used to simulate the enrofloxacin (ENR) elimination dynamic in deeper water of aquaculture. Two factors at values common in fishery water (temperature of 20°C, 25°C, and 30°C; pH of 5, 7, and 9) were studied. The degradation of ENR in the nine treatment groups ranged from 44.7 to 80.1%. Variance analysis indicated that pH had a strong impact on the elimination of ENR, while temperature changes showed little effect. The ENR removal rate was highest at a combination of 25°C and pH 5. The optimal conditions of eliminating ENR were performed for exploring the generation of ciprofloxacin (CIP), which indicated that higher ENR concentrations led to the production of greater amounts of CIP. The half-time of ENR was increased 2.02-times in the ENR concentrations increasing from 20 to 2000ng/mL. This study could increase our understanding of the behaviors of ENR and CIP during the aquaculture process.

Enrofloxacin pharmacokinetics in Takifugu flavidus after oral administration at three salinity levels

The present study was designed to explore the pharmacokinetics of enrofloxacin in Takifugu flavidus at different salinity levels (10‰, 20‰ and 30‰). The concentrations of enrofloxacin in plasma and tissues (kidney, liver and muscle) of T. flavidus after a single oral dose of 10 mg kg−1 were simultaneously determined using HPLC. The parameters of pharmacokinetics were calculated using non-compartmental model based on statistic moment theory. The peak concentrations of enrofloxacin were higher and Tmax values in plasma, liver and muscle tissues of T. flavidus were lower at the salinity of 20‰ and 30‰ than that of 10‰, except the kidney tissue. These demonstrated the absorption of enrofloxacin was more quickly and more quantity at the high salinity. The elimination half-life (t1/2z) of enrofloxacin in the plasma (45.22, 69.91 and 95.45 h) was increasing with the increase in salinity. And the t1/2z values of enrofloxacin in liver (76.44, 44.21 and 33.48 h) and kidney (212.16, 157.43 and 35.61 h) both decline with the increase in salinity, indicating the elimination of enrofloxacin was faster in liver and kidney but slower in plasma at the high salinity. The content of enrofloxacin in liver was increasing with the increase in salinity, suggesting that salinity affects tissue distribution and metabolism in T. flavidus. In addition, the AUC0–∞ data of enrofloxacin (kidney > plasma > liver > muscle) at different salinity levels were essentially consistent, and AUC0–∞ data of kidney were declined with the increase in salinity, supporting that the kidney was the main organ and the role of extent of kidney on excretion was different in different salinity levels.

Comparative pharmacokinetics of enrofloxacin in healthy and Aeromonas hydrophila‐infected crucian carp (Carassius auratus gibelio)

The comparative pharmacokinetics of enrofloxacin (ENR) and its metabolite ciprofloxacin (CIP) were investigated in healthy and Aeromonas hydrophila-infected crucian carp after a single oral (p.o.) administration at a dose of 10mg/kg at 25°C. The plasma concentrations of ENR and of CIP were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR concentrations by noncompartmental modeling. In healthy fish, the elimination half-life (T1/2λz ), maximum plasma concentration (Cmax ), time to peak (Tmax ), and area under the concentration-time curve (AUC) values were 64.66h, 3.55μg/mL, 0.5h, and 163.04μg·h/mL, respectively. In infected carp, by contrast, the corresponding values were 73.70h, 2.66μg/mL, 0.75h, and 137.43μg·h/mL, and the absorption and elimination of ENR were slower following oral administration. Very low levels of CIP were detected, which indicates a low extent of deethylation of ENR in crucian carp.

Effects of inducers of cytochrome P450s on enrofloxacin N-deethylation in crucian carp Carassius auratus gibelio.

In this study with crucian carp (Carassius auratus gibelio), the effect on enrofloxacin (EF) and its metabolite ciprofloxacin (CF) and on the activity of cytochrome P450 1A (CYP1A) and cytochrome P450 3A (CYP3A) was estimated following the oral administration of rifampicin (RIF) (12mg/kg) and β-naphthoflavone (BNF) (12mg/kg), respectively. First, reversed-phase high-performance liquid chromatography (RP-HPLC) was used to detect the pharmacokinetics of EF with continual blood sampling. In RIF-treated, BNF-treated and control groups, the value of the CmaxCF/CmaxEF ratio was 4.41, 0.81 and 0.95, and the corresponding value of the AUC0-t-CF/AUC0-t-EF ratio was 3.69, 1.84 and 1.76, respectively. In the RIF-treated, BNF-treated and control groups, the MRT values of EF were 26.57, 27.45 and 30.88h, and the corresponding values for CF were 5.79, 35.18 and 38.11h, respectively. Based on these results for crucian carp, the accumulation and elimination of EF and CF in the RIF-treated group were more rapid than in BNF-treated and control groups. Second, liver microsomes were pretreated with the inducer of CYP1A for BNF and that of CYP3A for RIF, and then the enzymatic activities of CYP1A and CYP3A were measured, respectively. The activities of ethoxyresorufin-O-deethylation (EROD) and erythromycin-N-demethylation (ERND) increased significantly (P<0.05) for CYP1A and CYP3A, respectively. However, in further experiments on the formation of CF, the level of EF N-deethylation was significantly induced by RIF and inhibited by ketoconazole (KTZ) for CYP3A but had no influence for CYP1A, BNF and berberine chloride (BER). We concluded that CYP3A might be responsible for the N-deethylation of EF and because of this activity, could also serve as a toxicity biomarker in crucian carp.

Elimination of enrofloxacin in striped catfish (Pangasianodon hypophthalmus) following on-farm treatment

article i nfo Enrofloxacin (ENR) has been widely used to treat bacterial infections in catfish aquaculture. However, little is known about the elimination of ENR in fish following treatment in aquaculture ponds. The aim of this study was through on-farm trials to establish the withdrawal period for ENR following treatment of striped catfish (Pangasianodon hypophthalmus). Three catfish ponds were treated daily for five consecutive days with medicated pelleted feed containing ENR (10 mg/kg body weight) following normal farmer procedures. Sampling of catfish muscle/skin for residue anal- ysis was done one day before the first feeding with medicated feed as well as three times during and five times after (7, 15, 30, 45, and 200 days) application of medicated feed. ENR and its metabolite ciprofloxacin (CIP) residues were analyzed by Liquid Chromatography coupled to Mass Spectrometry (LC-MS/MS). As expected, ENR and CIP residues initially accumulated in mixed muscle/skin and the concentrations were subsequently reduced during the sampling period. After 45 days (D45), the concentration of total ENR and CIP was 30.8 ± 4.1 μg/kg. Our results show that a withdrawal time of 45 days is sufficient for striped catfish treated with ENR, i.e. below the Maximum Residue Limit (MRL) assigned by the Commission of the European Commu- nities (100 μg/kg) in fish for human consumption but above the action level proposed by the US Food and Drug Administration (FDA) (5 μg/kg). Further, the 30-days withdraw period declared on the ENR products sold to catfish farmers is inadequate. The ENR and CIP residues found in skin about 200 days after treatment

Accumulation and elimination of enrofloxacin and its metabolite ciprofloxacin in the ridgetail white prawnExopalaemon carinicaudafollowing medicated feed and bath administration

Accumulation and elimination of enrofloxacin and its metabolite ciprofloxacin were evaluated in Exopalaemon carinicauda following medicated feed at dose of 10mg/kg weight body per day for five consecutive days and 10mg/L bath for five consecutive days at 18°C. At different times, nine ridgetail white prawns were randomly selected from the tank and sampled after the last medicated feed or bath administration. The concentration of enrofloxacin and ciprofloxacin in the main tissues (hepatopancreas, muscle, gill, and ovary) was detected by HPLC. The results showed that the maximum concentrations of enrofloxacin were 3.408±0.245, 0.554±0.088, 0.789±0.074, and 0.714±0.123μg/g for hepatopancreas, muscle, gill, and ovary, respectively, at 1day after the last medicated feed treatment. The enrofloxacin concentrations were 2.389±0.484, 0.656±0.012, 0.951±0.144, and 3.107±0.721μg/g in hepatopancreas, muscle, gill, and ovary, respectively, at 1day after the last bath administration. Ciprofloxacin could be detected in hepatopancreas, muscle, gill, and ovary. However, the concentrations of ciprofloxacin were much lower in comparison with that of enrofloxacin in various tissues. The concentrations of enrofloxacin plus ciprofloxacin in hepatopancreas, muscle, gill, and ovary followed an eliminating pattern during the sampling time after the two routes of administration. Based on data derived from this study, to avoid the enrofloxacin and ciprofloxacin residue in E.carinicauda, it should take at least 20 and 25days to wash out the drug from the tissues after the last medicated feed and bath administration with enrofloxacin, respectively. These results helped the Chinese fishery department to lay down the current guidelines on enrofloxacin plus ciprofloxacin withdrawal periods for farmed shrimp.

Pharmacokinetics of ciprofloxacin in animals

Ciprofloxacin is absorbed primarily from the duodenum and jejunum when administered orally to monogastric animals. Bioavailability from parenteral injection sites is nearly 100 percent for all fluoroquinolones in most cases. Enrofloxacin (Congener of ciprofloxacin) penetrates into milk to attain approximately twice the maximum concentration of ciprofloxacin at similar plasma concentrations, although the elimination of enrofloxacin from mild is approximately twice as fast as that of ciprofloxacin. The article highlights the proper dose, route of administration, pharmacokinetic parameters of animals as well as recommended dosages of ciprofloxacin in animals.

Accumulation and Elimination of Enrofloxacin and Ciprofloxacin in Tissues of Shrimp Litopenaeus vannamei under Laboratory and Farm Conditions.

This study aimed to quantify the accumulation and elimination of Enrofloxacin (ENRO) and Ciprofloxacin (CIPRO) in cultivated Litopenaeus vannamei under controlled laboratory and farm conditions. Laboratory- and farm-raised shrimp were given feed supplemented with 200 mg/kg ENRO for 14 days, followed by a 16-day diet without antibiotics. The levels of ENRO and CIPRO were analyzed by High Performance Liquid Chromatography (HPLC). In the laboratory, ENRO concentrations in the muscle and hepatopancreas reached a maximum (Cmax) of 0.54 ± 0.26 μg/g and 3.52 ± 1.9 μg/g, respectively; Cmax values for CIPRO in the laboratory were 0.18 ± 0.13 μg/g (muscle) and 1.05 ± 0.20 μg/g (hepatopancreas). In farmed shrimp, Cmax values for ENRO were 0.36 ± 0.17 μg/g muscle and 1.60 ± 0.82 μg/g in the hepatopancreas; CIPRO Cmax values were 0.03 ± 0.02 μg/g (muscle) and 0.36 ± 0.08 μg/g (hepatopancreas). Two to fourteen days were necessary to eliminate both antibiotics from muscular tissue and four to more fourteen days for complete elimination of the antibiotics from the hepatopancreas. These results should be considered in terms of minimum concentrations necessary to inhibit Vibrio bacteria to determine whether the current use of this antibiotic is effective in controlling disease.

The Effect of Temperature and Salinity on the Elimination of Enrofloxacin in the Manila Clam Ruditapes philippinarum

The effect of temperature and salinity on the elimination of enrofloxacin (EF) in Manila clams Ruditapes philippinarum was investigated. The clams, cultured under different temperatures and salinities (16 degrees C and 30 per thousand, 22 degrees C and 30 per thousand, or 22 degrees C and 20 per thousand), were exposed to EF at 5 microg/mL of water in a medicated bath. After a 24-h exposure, the concentration of EF in various tissues was measured by high-performance liquid chromatography and the elimination rate of EF in those tissues was investigated by regression analysis. After the treatment, the initial concentrations of EF among tissues were (in decreasing order) plasma > gill > visceral mass > foot > adductor muscle. In all tissues the elimination half-life (t1/2) of EF in the clams cultured at 22 degrees C and 20 per thousand and 16 degrees C and 30 per thousand were markedly longer than in those cultured at 22 degrees C and 30 per thousand, and the t1/2 at 16 degrees C and 30 per thousand was slightly longer than that at 22 degrees C and 20 per thousand. Slight differences were also observed in t1/2 values among various tissues. These data indicate that both temperature and salinity had significant effects on the elimination of EF in the Manila clams and that lower temperature or salinity could result in slower elimination.

Nonlinear toxicokinetics of enrofloxacin in rats

The dose-dependent toxicokinetics of enrofloxacin were studied by administering various single subcutaneous doses (5, 10, 20, 40, 70, 100, 150, 200, 300 and 400 mg/kg) in male Sprague-Dawley rats. The blood samples were collected from the tail veins, and the plasma concentration of enrofloxacin was determined by an HPLC-fluorescence detection (FLD) method. The time-concentration profiles of enrofloxacin were well fitted by an one-compartmental model with first order elimination. The absorption half-lives (t₁(/)₂(abs)) ranged from 0.2-0.8 h, and the mean time to maximum plasma concentration (T(max)) ranged from 0.6-1.8 h. On the other hand, marked disproportionate increases of the area under the curve (AUC) and elimination half-lives (t₁(/)₂) were observed from the increase of the doses. This result indicates that the elimination of enrofloxacin has nonlinear pharmacokinetic properties with increasing doses. Therefore, we need to take into consideration the possible occurrence of side effects resulting from greater systemic exposure from high dose therapies.

Study on the pharmacokinetics of enrofloxacin in the Chinese mitten-handed crab,Eriocheir sinensis, after different administration regimes

A pharmacokinetic study on enrofloxacin (ENR) following different administration regimes (i.e. intramuscular, oral and bath administrations) was carried out for the Chinese mitten-handed crab (Eriocheir sinensis) at 17 °C water temperature. Muscle and hepatopancreas samples were collected at each sampling time of 1 and 10 min and 0.5, 1, 2, 8, 16, 24, 48, 72 and 168 h for intramuscular administration and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 h for oral and bath administration. The levels of ENR and ciprofloxacin (CIP) were simultaneously determined (n=5) by high-performance liquid chromatography. The results showed that similar absorption and elimination patterns of ENR level in muscle and hepatopancreas were observed for oral administration and bath treatment; however, the trend in ENR level changes in muscle and hepatopancreas after intramuscular administration was quite different from oral and bath treatments. Meanwhile, the level of ENR in hepatopancreas was much higher than that in muscle for the same administration regimes. The concentration–time data were analysed with the Practical Pharmacokinetics Program (3P97), and the kinetic profiles of ENR in the hepatopancreas and muscle conformed to two-compartment models. The absorption and elimination of ENR in hepatopancreas for bath treatment were faster than those for oral and intramuscular administrations. However, the pattern was quite different in muscle. The fastest absorption and elimination of ENR in muscle were seen for intramuscular administration.