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PubMed2002

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in goats given enrofloxacin alone and in combination with probenecid.

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats given enrofloxacin alone or in combination with probenecid. Enrofloxacin was administered i.m. at a dosage of 5 mg x kg(-1) alone or in conjunction with probenecid (40 mg x kg(-1), i.v.). Blood samples were drawn from the jugular vein at predetermined time intervals after drug injection. Plasma was separated and analysed simultaneously for enrofloxacin and ciprofloxacin by reverse-phase high performance liquid chromatography. The plasma concentration-time data for both enrofloxacin and ciprofloxacin were best described by a one-compartment open pharmacokinetic model. The elimination half-life (t(1/2beta)), area under the plasma concentration-time curve (AUC), volume of distribution (V(d(area))), mean residence time (MRT) and total systemic clearance (Cl(B)) were 1.39 h, 7.82 microg x h x mL, 1.52 L x kg(-1), 2.37 h and 802.9 mL x h(-1) x kg(-1), respectively. Enrofloxacin was metabolized to ciprofloxacin in goats and the ratio between the AUCs of ciprofloxacin and enrofloxacin was 0.34. The t(1/2beta), AUC and MRT of ciprofloxacin were 1.82 h, 2.55 microg x h x mL and 3.59 h, respectively. Following combined administration of probenecid and enrofloxacin in goats, the sum of concentrations of enrofloxacin and ciprofloxacin levels > or = 0.1 microg x mL(-1) persisted in plasma up to 12 h.Co-administration of probenecid did not affect the t(1/2beta), AUC, V(d (area)) and Cl(B) of enrofloxacin, whereas the values of t(1/2beta) (3.85 h), AUC (6.29 microg x h x mL), MRT (7.34 h) and metabolite ratio (0.86) of ciprofloxacin were significantly increased. The sum of both enrofloxacin and ciprofloxacin levels was > or = 0.1 microg x mL(-1) and was maintained in plasma up to 8 h in goats after i.m. administration of enrofloxacin alone. These data indicate that a 12 h dosing regime may be appropriate for use in goats.

Animals↗

PubMed2000

Effects of endotoxin-induced fever and probenecid on disposition of enrofloxacin and its metabolite ciprofloxacin after intravascular administration of enrofloxacin in goats.

Pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in normal, febrile and probenecid-treated adult goats after single intravenous (i.v.) administration of enrofloxacin (5 mg/kg). Pharmacokinetic evaluation of the plasma concentration-time data of enrofloxacin and ciprofloxacin was performed using two- and one-compartment open models, respectively. Plasma enrofloxacin concentrations were significantly higher in febrile (0.75-7 h) and probenecid-treated (5-7 h) goats than in normal goats. The sum of enrofloxacin and ciprofloxacin concentrations in plasma > or =0.1 microg /mL was maintained up to 7 and 8 h in normal and febrile or probenecid-treated goats, respectively. The t1/2beta, AUC, MRT and ClB of enrofloxacin in normal animals were determined to be 1.14 h, 6.71 microg .h/mL, 1.5 h and 807 mL/h/kg, respectively. The fraction of enrofloxacin metabolized to ciprofloxacin was 28.8%. The Cmax., t1/2beta, AUC and MRT of ciprofloxacin in normal goats were 0.45 microg /mL, 1.79 h, 1.84 microg .h/mL and 3.34 h, respectively. As compared with normal goats, the values of t1/2beta (1.83 h), AUC (11.68 microg ? h/mL) and MRT (2.13 h) of enrofloxacin were significantly higher, whereas its ClB (430 mL/h/kg) and metabolite conversion to ciprofloxacin (8.5%) were lower in febrile goats. The Cmax. (0.18 microg /mL) and AUC (0.99 microg .h/mL) of ciprofloxacin were significantly decreased, whereas its t1/2beta (2.75 h) and MRT (4.58 h) were prolonged in febrile than in normal goats. Concomitant administration of probenecid (40 mg/kg, i.v.) with enrofloxacin did not significantly alter any of the pharmacokinetic variables of either enrofloxacin or ciprofloxacin in goats.

Animals↗

PubMed2002

Plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin in dogs following single oral administration of enrofloxacin at 7.5, 10, or 20 mg/kg.

Plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin were monitored following oral administration of enrofloxacin at 7.5, 10, and 20 mg/kg to six healthy female bloodhounds using a randomized crossover design. Plasma samples were collected at various times over 24 hours following drug administration. Both the parent drug and its metabolite were detected by high-performance liquid chromatography, and plasma drug concentration-versus-time curves were subjected to noncompartmental pharmacokinetic analysis. Descriptive statistics were determined for each dosage, and comparisons were made among dosage groups for selected pharmacokinetic parameters. Increasing dosages of enrofloxacin resulted in increased plasma concentrations of both enrofloxacin and ciprofloxacin. Maximum concentration (Cmax) was 2.12 +/- 0.59, 2.1 +/- 0.34, and 4.74 +/- 1.05 mcg/ml for enrofloxacin and 1.30 +/- 0.31, 1.30 +/- 0.32, and 1.86 +/- 0.35 mcg/ml for ciprofloxacin when enrofloxacin was given at dosages of 7.5, 10, and 20 mg/kg, respectively. Cmax and area under the curve (AUC) for both enrofloxacin and ciprofloxacin were significantly greater at 20 mg/kg than at 7.5 and 10 mg/kg. Disappearance half-life was similar for all dosages, ranging from 4.6 to 5.2 hours for enrofloxacin and 8.8 to 10.7 hours for ciprofloxacin. Ciprofloxacin contributed up to 42% of the Cmax and up to 55% of the AUC of the total (enrofloxacin plus ciprofloxacin). For organisms with a minimum inhibitory concentration (MIC) of 0.5 mcg enrofloxacin/ml, an inhibitory quotient (IQ; Cmax:MIC) of 8 or more was achieved in plasma only at 20 mg/kg.

Administration, Oral↗

PubMed2001

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intramuscular administration of enrofloxacin in goats.

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats after a single intramuscular administration of enrofloxacin at 2.5 mg/kg body weight. The plasma concentrations of enrofloxacin and ciprofloxacin were determined simultaneously by a HPLC method. The peak concentrations (Cmax) of enrofloxacin (1.13 microg/ml) and ciprofloxacin (0.24 microg/ml) were observed at 0.8 and 1.2 h, respectively. The elimination half-life (t1/2beta), volume of distribution (Vd(area)), total body clearance (Cl(B)) and mean residence time (MRT) of enrofloxacin were 0.74 h, 1.42 L/kg, 1329 ml/h per kg and 1.54 h, respectively. The t1/2beta, area under the plasma concentration-time curve (AUC) and the MRT of ciprofloxacin were 1.38 h, 0.74 microg h/ml and 2.73 h, respectively. The metabolic conversion of enrofloxacin to ciprofloxacin was appreciable (36%) and the sum of the plasma concentrations of enrofloxacin and ciprofloxacin was maintained at or above 0.1 microg/ml for up to 4 h. Enrofloxacin appears to be useful for the treatment of goat diseases associated with pathogens sensitive to this drug.

Animals↗

PubMed2002

Comparative pharmacokinetics of enrofloxacin and tissue concentrations of parent drug and ciprofloxacin after intramuscular administrations of free and liposome-encapsulated enrofloxacin in rabbits.

Pharmacokinetic properties and tissue concentrations of enrofloxacin and ciprofloxacin were compared after intramuscular (i.m.) administrations of free and liposome-encapsulated enrofloxacin at the dose of 5 mg/kg body weight (bw). Twelve healthy adult New Zealand white rabbits were used in the experiment. Blood samples were obtained at 10, 20, 40, 60 and 90 min and 2, 4, 6, 8 and 12 h and tissue samples were collected 24 h after injection. Concentrations of drugs in serum were determined by high-performance liquid chromatography. Pharmacokinetics were best described by a two-compartment open model. Results indicated that absorption rate was slow, peak concentration was higher (P < 0.05), and the time to peak concentration (tmax congruent with 1.5 h) was significantly longer (P < 0.05) for liposome-encapsulated enrofloxacin (LEE) when compared with free enrofloxacin. Values of elimination half-life (t1/2beta = 12.9 h) and mean residence time (MRT = 17.6 h) of liposome-encapsulated enrofloxacin were longer (P < 0.05) and total clearance (Cl = 0.43 l/h/kg) was lower than those of free form. Moreover, the distribution volume at steady-state (Vd(ss) = 14.4 l/kg) of enrofloxacin administered encapsulated into liposomes was significantly higher (P < 0.05) than that of free enrofloxacin (FE). The tissue levels of enrofloxacin and ciprofloxacin after LEE injection were not different (P > 0.05) from FE. In conclusion, the result of present study suggest that LEE may be a beneficial and valuable formulation in the treatment of infectious diseases caused by sensitive pathogens in animals, providing sustained drug release from injection side and prolonged therapeutic serum concentrations after i.m. administration.

Animals↗

PubMed2002

Pharmacokinetics and endometrial tissue concentrations of enrofloxacin and the metabolite ciprofloxacin after i.v. administration of enrofloxacin to mares.

Enrofloxacin was administered i.v. to five adult mares at a dose of 5 mg/kg. After administration, blood and endometrial biopsy samples were collected at regular intervals for 24 h. The plasma and tissue samples were analyzed for enrofloxacin and the metabolite ciprofloxacin by high-pressure liquid chromatography. In plasma, enrofloxacin had a terminal half-life (t(1/2)), volume of distribution (area method), and systemic clearance of 6.7 +/- 2.9 h, 1.9 +/- 0.4 L/kg, and 3.7 +/- 1.4 mL/kg/min, respectively. Ciprofloxacin had a maximum plasma concentration (Cmax) of 0.28 +/- 0.09 microg/mL. In endometrial tissue, the enrofloxacin Cmax was 1.7 +/- 0.5 microg/g, and the t(1/2) was 7.8 +/- 3.7 h. Ciprofloxacin Cmax in tissues was 0.15 +/- 0.04 microg/g and the t(1/2) was 5.2 +/- 2.0 h. The tissue:plasma enrofloxacin concentration ratios (w/w:w/v) were 0.175 +/- 0.08 and 0.47 +/- 0.06 for Cmax and AUC, respectively. For ciprofloxacin, these values were 0.55 +/- 0.13 and 0.58 +/- 0.31, respectively. We concluded that plasma concentrations achieved after 5 mg/kg i.v. are high enough to meet surrogate markers for antibacterial activity (Cmax:MIC ratio, and AUC:MIC ratio) considered effective for most susceptible gram-negative bacteria. Endometrial tissue concentrations taken from the mares after dosing showed that enrofloxacin and ciprofloxacin both penetrate this tissue adequately after systemic administration and would attain concentrations high enough in the tissue fluids to treat infections of the endometrium caused by susceptible bacteria.

Animals↗

PubMed1995

Enrofloxacin-theophylline interaction: influence of enrofloxacin on theophylline steady-state pharmacokinetics in the beagle dog.

Enrofloxacin, a quinolone antibiotic developed exclusively for use in animals, was investigated for its effects on the steady-state pharmacokinetics of theophylline in six healthy Beagle dogs. A sustained-release theophylline formulation was given alone (20 mg/kg per os twice daily at 12 h intervals) for 9 days and then co-administered with enrofloxacin (5 mg/kg i.v. once a day) for 5 days. Mean trough theophylline concentrations progressively and significantly increased during the five days of enrofloxacin co-administration. Theophylline clearance and concentration-time profile were significantly changed by enrofloxacin co-administration. No significant change was observed in enrofloxacin pharmacokinetics. The kinetic interaction between theophylline and enrofloxacin could be of clinical significance and may require plasma drug concentration monitoring and adjustment of theophylline dosage.

Administration, Oral↗

PubMed1993

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and oral administration of enrofloxacin in dogs.

Four dogs were given 5 mg/kg body weight enrofloxacin intravenously (i.v.) and orally (p.o.) in a cross-over study. Plasma concentrations of the active ingredient enrofloxacin and its main metabolite ciprofloxacin were determined by a reversed phase liquid chromatographic method. Pharmacokinetic parameters of both substances were calculated by use of statistical moments and were compared to those of enrofloxacin described in the veterinary literature. Mean enrofloxacin t1/2 lambda z was 2.4 h, mean Cls was 27.1 ml/min.kg, and mean Vss was 7.0 l/kg. After i.v. and p.o. administration, concentrations of ciprofloxacin exceeding minimal inhibitory concentrations of several microorganisms were reached (Cmax = 0.2 microgram/ml, tmax = 2.2 h after intravenous administration; Cmax = 0.2 microgram/ml, tmax = 3.6 h after oral administration). A considerable part of the antimicrobial activity is due to ciprofloxacin, the main metabolite of enrofloxacin.

Administration, Oral↗

PubMed1999

Pharmacokinetics of enrofloxacin and danofloxacin in plasma, inflammatory exudate, and bronchial secretions of calves following subcutaneous administration.

Enrofloxacin (2.5 mg/kg of body weight) and danofloxacin (1.25 mg/kg) were administered subcutaneously to ruminating calves (n = 8) fitted with subcutaneous tissue cages. Concentrations of enrofloxacin, its metabolite ciprofloxacin, and danofloxacin in blood (plasma), tissue cage exudate (following intracaveal injection of 0.3 ml of 1% [vol/wt] carrageenan), and bronchial secretions were measured by high-performance liquid chromatography (HPLC) and microbiological assay (enrofloxacin plus ciprofloxacin and danofloxacin). Mean maximum concentrations (C(max)) +/- standard deviations of enrofloxacin (0.24 +/- 0.08 microg/ml), ciprofloxacin (0.11 +/- 0.03 [total, 0.34 +/- 0.10] microg/ml), and danofloxacin (0.23 +/- 0.05 microg/ml) were detected in the plasma of calves by HPLC. The C(max) were 0.49 +/- 0.17 microg/ml (enrofloxacin equivalents) and 0.24 +/- 0.03 microg/ml (danofloxacin) when they were measured by microbiological assay. Mean C(max) in exudate (HPLC) were 0.18 +/- 0.07 microg/ml (enrofloxacin), 0.10 +/- 0.04 microg/ml (ciprofloxacin), 0.27 +/- 0.09 microg/ml (enrofloxacin plus ciprofloxacin), and 0.19 +/- 0.05 microg/ml (danofloxacin), and concentrations in exudate exceeded those in plasma from 8 h (enrofloxacin and ciprofloxacin) or 6 h (danofloxacin) after drug administration. The C(max) were 0.34 +/- 0.09 microg/ml (enrofloxacin equivalents) and 0.22 +/- 0.04 microg/ml (danofloxacin) in exudate when they were measured by the microbiological assay. The maximum mean concentration achieved in bronchial secretions (HPLC) were 0.07 +/- 0.04 microg/ml (enrofloxacin), 0.04 +/- 0.07 microg/ml (ciprofloxacin), 0.10 +/- 0. 05 microg/ml (enrofloxacin plus ciprofloxacin), and 0.12 +/- 0.09 microg/ml (danofloxacin). The maximum mean concentration in bronchial secretions from a limited number of animals from which samples were available for microbiological assay were 0.27 +/- 0.11 microg/ml (n = 4 [enrofloxacin equivalents]) and 0.14 +/- 0.02 microg/ml (n = 3 [danofloxacin]). With predictive models of efficacy (C(max)/MIC and area under the concentration-time curve/MIC ratios in plasma) for Pasteurella multocida (MIC of enrofloxacin, 0.06 microg/ml [24]; MIC of danofloxacin, 0.06 microg/ml [6]), enrofloxacin produced scores of 8.17 and 52.00, respectively, compared to those of danofloxacin, which were 4.02 and 23.05, respectively. With the dosing rates recommended in some markets by manufacturers, enrofloxacin and danofloxacin achieved concentrations above the MICs for important pathogenic organisms in plasma, tissue cage exudate, and bronchial secretion. Since fluoroquinolones display concentration-dependent activities, C(max)/MIC ratios may be critical to efficacy. In the United States enrofloxacin is currently the only fluoroquinolone licensed for food animals and dosages for acute respiratory disease are 2.5 to 5 mg/kg for 3 days or 7.5 to 12. 5 mg/kg once. The higher dosages on a single occasion are likely to confer C(max)/MIC ratios that are associated with greater clinical efficacy.

Animals↗

PubMed1999

Effects of enrofloxacin on porcine phagocytic function.

The interaction between enrofloxacin and porcine phagocytes was studied with clinically relevant concentrations of enrofloxacin. Enrofloxacin accumulated in phagocytes, with cellular concentration/extracellular concentration ratios of 9 for polymorphonuclear leukocytes (PMNs) and 5 for alveolar macrophages (AMs). Cells with accumulated enrofloxacin brought into enrofloxacin-free medium released approximately 80% (AMs) to 90% (PMNs) of their enrofloxacin within the first 10 min, after which no further release was seen. Enrofloxacin affected neither the viability of PMNs and AMs nor the chemotaxis of PMNs at concentrations ranging from 0 to 10 microg/ml. Enrofloxacin (0.5 microg/ml) did not alter the capability of PMNs and AMs to phagocytize fluorescent microparticles or Actinobacillus pleuropneumoniae, Pasteurella multocida, and Staphylococcus aureus. Significant differences in intracellular killing were seen with enrofloxacin at 5x the MIC compared with that for controls not treated with enrofloxacin. PMNs killed all S. aureus isolates in 3 h with or without enrofloxacin. Intracellular S. aureus isolates in AMs were less susceptible than extracellular S. aureus isolates to the bactericidal effect of enrofloxacin. P. multocida was not phagocytosed by PMNs. AMs did not kill P. multocida, and similar intra- and extracellular reductions of P. multocida isolates by enrofloxacin were found. Intraphagocytic killing of A. pleuropneumoniae was significantly enhanced by enrofloxacin at 5x the MIC in both PMNs and AMs. AMs are very susceptible to the A. pleuropneumoniae cytotoxin. This suggests that in serologically naive pigs the enhancing effect of enrofloxacin on the bactericidal action of PMNs may have clinical relevance.

Actinobacillus pleuropneumoniae↗

PubMed1997

A comprehensive model for enrofloxacin to ciprofloxacin transformation and disposition in dog.

The pharmacokinetics of enrofloxacin and ciprofloxacin, its major active metabolite, were determined in dog after oral and intravenous administrations of enrofloxacin and intravenous infusion of ciprofloxacin. A comprehensive model of enrofloxacin and ciprofloxacin disposition was constructed to investigate the extent of enrofloxacin to ciprofloxacin transformation and the influence of the hepatic first-pass effect on the parent compound oral bioavailability. Plasma levels were measured using a validated HPLC method. Enrofloxacin and ciprofloxacin plasma concentration data were fitted simultaneously using a set of differential equations describing a six-compartment model (two compartments for each analyte, one for the liver, and one for the intestinal tract); it was assumed that only a fraction of enrofloxacin was metabolized to ciprofloxacin and that this conversion only occurred in the liver. The fitted parameters obtained from the model were used to calculate plasma clearances (0.729 +/- 0.212 L/h/kg for enrofloxacin, 0.468 +/- 0.094 L/h/kg for ciprofloxacin), distribution volumes (2.45 +/- 0.49 L/kg for enrofloxacin, 1.92 +/- 0.33 L/kg for ciprofloxacin), mean residence times (3.47 +/- 0.78 h for enrofloxacin, 4.20 +/- 0.82 h for ciprofloxacin), and the fractions of enrofloxacin metabolized to ciprofloxacin after intravenous and oral administrations of enrofloxacin. It was shown that enrofloxacin was largely metabolized to ciprofloxacin and that the fractions of metabolized enrofloxacin were similar after intravenous and oral administrations of enrofloxacin (40.44 +/- 10.08 and 40.17 +/- 8.33%, respectively), the hepatic first-pass effect being low (7.15 +/- 1.99%).

Administration, Oral↗

PubMed2004

Interaction between enrofloxacin and monensin in broiler chickens.

Enrofloxacin, a fluoroquinolone, and its interaction with monensin, an ionophore drug, was studied to explore the influence of enrofloxacin on drug metabolizing enzymes that can lead to physiological and toxicological consequences upon coadministration with monensin in broiler chickens. Group I, treated with 100 mg monesin/kg feed from 1 d old to 41st d of age, did not show any influence on aniline hydroxylase and cytochrome b5 levels. Group II, treated with 10 mg enrofloxacin/kg body weight per os for three consecutive days on 33rd, 34th, 35th d of age, had a highly significant decrease in aniline hydroxylase on 38th d (ie on 3rd d post-treatment with enrofloxacin); a reversal effect was noticed on the 41st day (ie on 6th d post-treatment with enrofloxacin). There was no alteration in cytochrome b5 level. Group III with monensin and enrofloxacin coadministration 100 mg monensin/kg feed from 1 d old to the 41st day + 10 mg enrofloxacin/kg body weight, per os for 3 consecutive days on the 33rd, 34th, 35th d of age) had a significant decrease in aniline hydroxylase level on the 3rd d post-treatment with enrofloxacin, but an elevation tending to reach normal on the 6th d post-treatment with enrofloxacin. Monensin + enrofloxacin coadministration did not produce any alteration in cytochrome b5 level. Creatine kinase (CK) and alanine amino transferase (ALT) levels significantly increased on the 3rd d post-treatment with enrofloxacin, but on the 6th d post-treatment with enrofloxacin the increase declined. Aspartate amino transferase (AST) significantly increased on the 6th d post enrofloxacin treatment. This study demonstrated the reversible competitive type of inhibition of enrofloxacin on CYP450 enzymes, and with coadministration with monensin produced increased CK, AST and ALT serum enzymes suggesting heart and liver injury. Simultaneous administration of enrofloxacin and monensin even at recommended levels could result in adverse interactions.

Animals↗

PubMed1999

Pharmacokinetic variables and tissue residues of enrofloxacin and ciprofloxacin in healthy pigs.

OBJECTIVES: To determine pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after a single i.v. and i.m. administration of enrofloxacin and tissue residues after serial daily i.m. administration of enrofloxacin in pigs. ANIMALS: 20 healthy male pigs. PROCEDURE: 8 pigs were used in a crossover design to investigate pharmacokinetics of enrofloxacin after a single i.v. and i.m. administration (2.5 mg/kg of body weight). Twelve pigs were used to study tissue residues; they were given daily doses of enrofloxacin (2.5 mg/kg, i.m. for 3 days). Plasma and tissue concentrations of enrofloxacin and ciprofloxacin were determined. Residues of enrofloxacin and ciprofloxacin were measured in fat, kidney, liver, and muscle. RESULTS: Mean (+/-SD) elimination half-life and mean residence time of enrofloxacin in plasma were 9.64+/-1.49 and 12.77+/-2.15 hours, respectively, after i.v. administration and 12.06+/-0.68 and 17.15+/-1.04 hours, respectively, after i.m. administration. Half-life at alpha phase of enrofloxacin was 0.23+/-0.05 and 1.94+/-0.70 hours for i.v. and i.m. administration, respectively. Maximal plasma concentration was 1.17 +/-0.23 microg/ml, and interval from injection until maximum concentration was 1.81+/-0.23 hours. Renal and hepatic concentrations of enrofloxacin (0.012 to 0.017 microg/g) persisted for 10 days; however, at that time, ciprofloxacin residues were not detected in other tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered i.m. at a dosage of 2.5 mg/kg for 3 successive days, with a withdrawal time of 10 days, resulted in a sum of concentrations of enrofloxacin and ciprofloxacin that were less than the European Union maximal residue limit of 30 ng/g in edible tissues.

Animals↗

PubMed2003

Influence of albendazole on the disposition kinetics and milk antimicrobial equivalent activity of enrofloxacin in lactating goats.

The pharmacokinetics of single intravenous and intramuscular administrations and milk antimicrobial equivalent activity of enrofloxacin at a dose of 5 mg per kilogram body weight were studied in clinically healthy lactating goats which were either not treated or had received 7.5 mg per kilogram body weight of albendazole orally. The concentrations of enrofloxacin in serum and milk were determined using microbiological assay. Following intravenous injection, enrofloxacin antimicrobial equivalent activity versus time data in serum was described by a two-compartmental open model. Albendazole treatment significantly decreased the elimination half-life (t(1/2beta)) (P>or=0.05) and the mean residence time (MRT) (P>or=0.05), whereas, the rate of enrofloxacin return to central compartment from peripheral tissue (K(21)) was significantly increased (P>or=0.01). In contrast, the volumes of distribution V(d(area)) and V(d(SS)) were significantly decreased (P>or=0.01 and P>or=0.05, respectively) in albendazole-treated goats. After intramuscular injection, enrofloxacin was rapidly absorbed in control and albendazole-treated lactating goats with absorption half-lives (t(1/2ab)) 0.43 and 0.39 h, respectively. The mean peaks of serum concentration (C(max)) were 0.68 and 0.65 mcg ml(-1) attained at (t(max)) 1.08 and 1.12 h, before and after albendazole dosing, respectively. The elimination half-life (t(1/2el)) and (MRT) following intramuscular injections were also shorter in the albendazole-treated lactating goats. The systemic bioavailability of enrofloxacin was significantly decreased from 110.16 to 84.38% in albendazole-treated lactating goats. Concomitant administration of albendazole with enrofloxacin resulted in significant alterations in the disposition kinetic of enrofloxacin and significant decrease in enrofloxacin concentrations in milk. Consequently, the interaction between albendazole and enrofloxacin could be of clinical significance and may require monitoring and adjustment of enrofloxacin dosage.

Administration, Oral↗

PubMed2002

Pharmacokinetics after intravenous and oral administration of enrofloxacin in sheep.

OBJECTIVE: To compare pharmacokinetics of enrofloxacin administered IV and in various oral preparations to ewes. ANIMALS: 5 mature Katahdin ewes weighing 42 to 50 kg. PROCEDURE: Ewes received 4 single-dose treatments of enrofloxacin in a nonrandomized crossover design followed by a multiple-dose oral regimen. Single-dose treatments consisted of an IV bolus of enrofloxacin (5 mg/kg), an oral drench (10 mg/kg) made from crushed enrofloxacin tablets, oral administration in feed (10 mg/kg; mixture of crushed enrofloxacin tablets and grain), and another type of oral administration in feed (10 mg/kg; mixture of enrofloxacin solution and grain). The multiple-dose regimen consisted of feeding a mixture of enrofloxacin solution and grain (10 mg/kg, q 24 h, for 7 days). Plasma concentrations of enrofloxacin and ciprofloxacin were measured by use of high-performance liquid chromatography. RESULTS: Harmonic mean half-life for oral administration was 14.80, 10.80, and 13.07 hours, respectively, for the oral drench, crushed tablets in grain, and enrofloxacin solution in grain. Oral bioavailability for the oral drench, crushed tablets in grain, and enrofloxacin in grain was 4789, 98.07, and 94.60%, respectively, and median maximum concentration (Cmax) was 1.61, 2.69, and 2.26 microg/ml, respectively. Median Cmax of the multiple-dose regimen was 2.99 microg/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered orally to sheep has a prolonged half-life and high oral bioavailability. Oral administration at 10 mg/kg, q 24 h, was sufficient to achieve a plasma concentration of 8 to 10 times the minimum inhibitory concentration (MIC) of any microorganism with an MIC < or = 0.29 microg/ml.

Administration, Oral↗

PubMed2004

The effects of enrofloxacin on decorin and glycosaminoglycans in avian tendon cell cultures.

Tendonitis and tendon rupture have been reported to occur during or following therapy with fluoroquinolone antibiotics. Though the pathogenesis is unknown, several studies suggest that fluoroquinolone antibiotics alter proteoglycan content in soft tissues, including tendons, and thereby alter collagen fibrillogenesis. To better understand the mechanism of action of fluoroquinolones, we studied the effects of enrofloxacin, a widely used fluoroquinolone in veterinary medicine, on avian tendon cell cultures established from gastrocnemius tendons from 18-day-old chicken embryos. We found that cell proliferation was progressively inhibited with increasing concentrations of enrofloxacin. This was accompanied by changes in morphology, extracellular matrix content and collagen fibril formation as detected by electron microscopy. We also observed a 35% decrease in the content of total monosaccharides in enrofloxacin-treated cells. The ratio of individual monosaccharides was also altered in enrofloxacin-treated cells. Enrofloxacin also induced the synthesis of small amounts of keratan sulfate in tendon cells. Moreover we observed enrofloxacin-induced changes in glycosylation of decorin, the most abundant tendon proteoglycan, resulting in the emergence of multiple lower molecular bands that were identifiable as decorin after chondroitinase ABC and N-glycanase treatment of extracts from enrofloxacin-treated cells. Medium conditioned by enrofloxacin-treated cells contained less decorin than did medium conditioned by control cells. We hypothesize that enrofloxacin induces either changes in the number of N-linked oligosaccharides attached to the core protein of decorin or changes in decorin degradation process. In conclusion, our data suggest that enrofloxacin affects cell proliferation and extracellular matrix through changes in glycosylation.

Animals↗

PubMed1999

Comparative study of the plasma pharmacokinetics and tissue concentrations of danofloxacin and enrofloxacin in broiler chickens.

The plasma pharmacokinetics of danofloxacin and enrofloxacin in broiler chickens was investigated following single intravenous (i.v.) or oral administration (p.o.) and the steady-state plasma and tissue concentrations of both drugs were investigated after continuous administration via the drinking water. The following dosages approved for the treatment of chickens were used: danofloxacin 5 mg/kg and enrofloxacin 10 mg/kg of body weight. Concentrations of danofloxacin and enrofloxacin including its metabolite ciprofloxacin were determined in plasma and eight tissues by specific and sensitive high performance liquid chromatography methods. Pharmacokinetic parameter values for both application routes calculated by noncompartmental methods were similar for danofloxacin compared to enrofloxacin with respect to elimination half-life (t1/2: approximately 6-7 h), mean residence time (MRT; 6-9 h) and mean absorption time (MAT; 1.44 vs. 1.20 h). However, values were twofold higher for body clearance (ClB; 24 vs. 10 mL/min. kg) and volume of distribution at steady state (VdSS; 10 vs. 4 L/kg). Maximum plasma concentration (Cmax) after oral administration was 0.5 and 1.9 micrograms/mL for danofloxacin and enrofloxacin, respectively, occurring at 1.5 h for both drugs. Bioavailability (F) was high: 99% for danofloxacin and 89% for enrofloxacin. Steady-state plasma concentrations (mean +/- SD) following administration via the drinking water were fourfold higher for enrofloxacin (0.52 +/- 0.16 microgram/mL) compared to danofloxacin (0.12 +/- 0.01 microgram/mL). The steady-state AUC0-24 h values of 12.48 and 2.88 micrograms.h/mL, respectively, derived from these plasma concentrations are comparable with corresponding area under the plasma concentration-time curve (AUC) values after single oral administration. For both drugs, tissue concentrations markedly exceeded plasma concentrations, e.g. in the target lung, tissue concentrations of 0.31 +/- 0.07 microgram/g for danofloxacin and 0.88 +/- 0.24 microgram/g for enrofloxacin were detected. Taking into account the similar in vitro activity of danofloxacin and enrofloxacin against important pathogens in chickens, a higher therapeutic efficacy of water medication for enrofloxacin compared to danofloxacin can be expected when given at the approved dosages.

Administration, Oral↗

PubMed2004

Therapeutic efficacy of bacteriophage and Baytril (enrofloxacin) individually and in combination to treat colibacillosis in broilers.

A study was conducted to evaluate the therapeutic efficacy of bacteriophage and the antibiotic enrofloxacin individually and in combination to treat colibacillosis. The experimental design was a 2 x 2 x 2 factorial with 8 treatments and 4 replicate pens of 10 birds. The treatments were 1) control, 2) unchallenged birds treated with bacteriophage, 3) enrofloxacin, or 4) the combination; 5) birds challenged with Escherichia coli, and birds challenged with E. coli and treated with 6) bacteriophage, 7) enrofloxacin, or 8) the combination of bacteriophage and enrofloxacin. Birds in the E. coli challenged treatments were challenged at 7 d of age by injecting 10(4) cfu of E. coli into the thoracic air sac. The antibiotic treatment was initiated immediately after the birds were challenged and consisted of 50 ppm enrofloxacin in the drinking water for 7 consecutive days. The bacteriophage treatment consisted of a single intramuscular injection of 2 different bacteriophage (10(9) pfu) administered immediately after the E. coli challenge. Mortality in the birds challenged with E. coli and untreated was 68%, and the bacteriophage and enrofloxacin treatments significantly decreased mortality to 15 and 3%, respectively. There was total protection in birds that received both the bacteriophage and enrofloxacin representing a significant synergy. The decrease in mortality with enrofloxacin (3%) was significantly better than the decrease in mortality with bacteriophage (15%). Airsacculitis lesion scores and lesion incidence in surviving birds were significantly less in the enrofloxacin treatment compared with the bacteriophage treatment. Both bacteriophage and enrofloxacin provided effective treatments of colibacillosis, and the synergy between these 2 treatments suggests that bacteriophage combined with antibiotic treatment has significant value.

Animals↗