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1.
BACKGROUND: Fluoroquinolones are often used interchangeably in dogs and cats. HYPOTHESIS: Predicted therapeutic efficacy differs among fluoroquinolones. ANIMALS: Bacterial pathogens isolated from dogs and cats. METHODS: Using microtube-dilution procedures, percent resistance and 2 pharmacodynamic/pharmacokinetic indices (maximum concentration/minimum inhibitory concentration [Cmax/MIC] [target 0.10] and area under curve/minimum inhibitory concentration [AUC/MIC] [target 0.125]) were compared prospectively at low and high doses (mg/kg) for ciprofloxacin (5 and 20), difloxacin (5 and 10), enrofloxacin (including enrofloxacin+ciprofloxacin) (5 and 20), marbofloxacin (2.5 and 5), and orbifloxacin (2.5 and 7.5). Indices were calculated for organisms represented by < or = 15 isolates. RESULTS: Percent resistance for all Gram-negative (n = 180; 20+/-3%; 39+/-5% for Escherichia coli) and Gram-positive isolates (n = 66; 18+/-3%) did not differ among drugs or organisms. The pattern of Cmax/MIC was generally enrofloxacin+ciprofloxacin > or = enrofloxacin or ciprofloxacin > or = marbofloxacin > or = orbifloxacin > or = difloxacin; and for AUIC/ MIC, enrofloxacin+ciprofloxacin > or = marbofloxacin > or = ciprofloxacin > or = enrofloxacin > difloxacin > orbifloxacin. Among susceptible Gram-negative isolates studied (n = 117), targeted Cmax/MIC or AUC/MIC were achieved in 88% of E. coli, 53% of Proteus mirabilis, and 35% of Pseudomonas aeruginosa; and for susceptible Gram-positive isolates studied (n = 49), 53% of Streptotoccus spp. and Staphylococcus intermedius and 27% of Staphylococcus spp. At the high dose, the proportion of isolates for which a target was reached was: ciprofloxacin, enrofloxacin+ciprofloaxin, and marbofloxacin (77%), enrofloxacin (73%), orbifloxacin (51%), and difloxacin (40%); and at the low dose, enrofloxacin+ciprofloxacin and enrofloxacin (43%), ciprofloxacin (40%), marbofloxacin (39%), orbifloxacin (29%), and difloxacin (28%). CONCLUSIONS: E. coli resistance to fluoroquinolones approximated 40%. For susceptible isolates, enrofloxacin, marbofloxacin, and ciprofloxacin more consistently reached indices associated with predicted efficacy, but only at the high dose.  相似文献   

2.
The antibacterial activity, selection of Escherichia coli (E. coli) mutants and mechanisms of fluoroquinolone resistance were investigated by integrating the minimum inhibitory concentration (MIC), mutant prevention concentration (MPC) and in vitro dynamic model approaches. Difloxacin and orbifloxacin, for which the above information has been scarce, were used. A range of area under curve over a 24h interval (AUC(24h))/MIC ratios and selected E. coli strains were investigated using the dynamic models. Continuous incubation for three days in the presence of difloxacin or orbifloxacin resulted in losses in E. coli susceptibility. An AUC(24h)/MIC (AUC(24h)/MPC)-dependent fluoroquinolone activity and selection of E. coli mutants was confirmed. Maximum losses in susceptibility occurred at AUC(24h)/MIC ratios of 54 (orbifloxacin) and 57.3 (difloxacin). AUC(24h)/MIC ratios of 169.8 (orbifloxacin) and 199.5 (difloxacin) were estimated to be protective against the selection of E. coli mutants, and the corresponding ratios based on AUC(24h)/MPC predictions were 34 (orbifloxacin) and 36.3 (difloxacin). When integrating our in vitro data with pharmacokinetic data in dogs, the conventional clinical doses of both drugs were found to be inadequate to attain the above protective values for 90% of the mutant subpopulation (AUC(24h)/MPC(90)). Both target mutations, esp. at codon 83 (Ser to Leu) of gyrA, and overexpression of efflux pumps contributed to resistance development, with mutants also showing decreased susceptibility to enrofloxacin and marbofloxacin. Additional studies would determine the role of mutations found outside the QRDR, at codon 24 of gyrA, and at codon 116 of parC, and establish the significance of these observations in vivo.  相似文献   

3.
Marbofloxacin is a fluoroquinolone antimicrobial drug used in cattle for the treatment of respiratory infections. In this investigation the pharmacokinetics (PK) of marbofloxacin were determined after intravenous and intramuscular dosing at a dosage of 2 mg/kg. In addition the ex vivo pharmacodynamics (PD) of the drug were determined in serum and three types of tissue cage fluid (transudate, inflammatory exudate generated by carrageenan and exudate generated by lipopolysaccharide). Marbofloxacin PK was characterized by a high volume of distribution after dosing by both routes (1.28 L/kg intravenous and 1.25 L/kg intramuscular). Corresponding area under the concentration-time curve (AUC) and elimination half-life (t(1/2)el) values were 9.99 and 10.11 microg h/mL and 4.23 and 4.33 h, respectively. Values of AUC for carrageenan-induced exudate, lipopolysaccharide-induced exudate and transudate were, respectively, 8.28, 7.83 and 7.75 microg h/mL after intravenous and 8.84, 8.53 and 8.52 microg h/mL after intramuscular dosing. Maximum concentration (Cmax) values were similar for the three tissue cage fluids after intravenous and intramuscular dosing. For in vivo PK data values of AUC: minimum inhibitory concentration (MIC) (AUIC) ratio for serum were 250 and 253, respectively, after intravenous and intramuscular dosing of marbofloxacin against a pathogenic strain of Mannheimia haemolytica (MIC=0.04 microg/mL). For all tissue cage fluids AUIC values were >194 and >213 after intravenous and intramuscular dosing, and Cmax/MIC ratios were 9 or greater, indicating a likely high level of effectiveness in clinical infections caused by M. haemolytica of MIC 0.04 microg/mL or less. This was confirmed by both in vitro (serum) and ex vivo (serum, exudate and transudate) measurements, which demonstrated a concentration-dependent killing profile for marbofloxacin against M. haemolytica. Ex vivo, after 24-h incubation, virtually all bacteria were killed (<10 cfu/mL) in all samples collected up to 9 h (serum), 24 h (carrageenan-induced exudate and transudate) and 36 h (lipopolysaccharide-induced exudate). Application of the sigmoid Emax equation to the ex vivo antibacterial data provided, for serum, AUIC24 h values of 37.1 for bacteriostasis, 46.3 for bactericidal activity and 119.6 for elimination of bacteria. These data may be used as a rational basis for setting dosing schedules which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms.  相似文献   

4.
Serum concentrations and pharmacokinetics of enrofloxacin were studied in 6 mares after intravenous (IV) and intragastric (IG) administration at a single dose rate of 7.5 mg/kg body weight. In experiment 1, an injectable formulation of enrofloxacin (100 mg/mL) was given IV. At 5 min after injection, mean serum concentration was 9.04 microg/mL and decreased to 0.09 microg/mL by 24 h. Elimination half-life was 5.33 +/- 1.05 h and the area under the serum concentration vs time curve (AUC) was 21.03 +/- 5.19 mg x h/L. In experiment 2, the same injectable formulation was given IG. The mean peak serum concentration was 0.94 +/- 0.97 microg/mL at 4 h after administration and declined to 0.29 +/- 0.12 microg/mL by 24 h. Absorption of this enrofloxacin preparation after IG administration was highly variable, and for this reason, pharmacokinetic values for each mare could not be determined. In experiment 3, a poultry formulation (32.3 mg/mL) was given IG. The mean peak serum concentration was 1.85 +/- 1.47 microg/mL at 45 min after administration and declined to 0.19 +/- 0.06 microg/mL by 24 h. Elimination half-life was 10.62 +/- 5.33 h and AUC was 16.30 +/- 4.69 mg x h/L. Bioavailability was calculated at 78.29 +/- 16.55%. Minimum inhibitory concentrations of enrofloxacin were determined for equine bacterial culture specimens submitted to the microbiology laboratory over an 11-month period. The minimum inhibitory concentration of enrofloxacin required to inhibit 90% of isolates (MIC90) was 0.25 microg/mL for Staphylococcus aureus, Escherichia coli, Salmonella spp., Klebsiella spp., and Pasteurella spp. The poultry formulation was well tolerated and could be potentially useful in the treatment of susceptible bacterial infections in adult horses. The injectable enrofloxacin solution should not be used orally.  相似文献   

5.
Background – The problem of antibacterial drug resistance is increasing worldwide, in part due to the therapeutic concentrations currently used based on the minimal inhibitory concentration (MIC) as a measure of potency are often the very concentrations required to selectively enrich the resistant mutant portion of the population. A mutant prevention concentration (MPC)‐based dosing strategy is suggested to improve the therapeutic outcome based on the MIC. Objective – Our aim was to investigate the MPC and mechanism of resistance to various fluoroquinolones using recent Staphylococcus pseudintermedius isolates from canine pyoderma. Methods – The broth microdilution method for MIC and a series of agar plates containing different concentrations of fluoroquinolones were inoculated with ～1010 colony‐forming units of the bacterial culture for MPC were used. PCR was used to identify mutation in the resistant isolates. Results – The rank order of potency based on MIC and MPC was ciprofloxacin = enrofloxacin ≥ marbofloxacin > difloxacin ≥ orbifloxacin. Integrating our data with reported pharmacokinetic data at the recommended dose ranges revealed that only high doses of ciprofloxacin, enrofloxacin and marbofloxacin could achieve a maximal plasma concentration (Cmax) greater than the MPC of 90% of isolates (Cmax/MPC90). The overall rank of potency against S. pseudintermedius, based on Cmax/MIC, Cmax/MPC, the area under concentration–time curve (AUC)/MIC and AUC/MPC values, was in decreasing order: enrofloxacin > ciprofloxacin ≥ marbofloxacin ≥ orbifloxacin = difloxacin. Sequencing of the quinolone resistant determining region of gyrA, gyrB, grlA and grlB of resistant strains showed a base‐pair substitution in both gyrA and gyrB that resulted in Ser‐84 to Leu and Ser‐80 to Arg amino acid changes, respectively. Conclusions and clinical importance – High doses of ciprofloxacin, enrofloxacin and marbofloxacin could minimize the selection of resistant mutants, whereas the possibility of selecting mutants with the conventional doses of difloxacin and orbifloxacin, and low clinical doses of all fluoroquinolones, seems high.  相似文献   

6.
Pharmacokinetics and distribution of orbifloxacin into body fluids and endometrium was studied in 6 mares after intragastric (IG) administration at a single dose rate of 7.5 mg/kg body weight. Orbifloxacin concentrations were serially measured in serum, synovial fluid, peritoneal fluid, urine, cerebrospinal fluid, and endometrial tissues over 24 hours. Minimum inhibitory concentrations of orbifloxacin were determined for 120 equine pathogens over an 11-month period. The mean peak serum concentration (Cmax) was 2.41+/-0.30 microg/mL at 1.5 hours after administration and decreased to 0.17+/-0.01 microg/mL (Cmin) at 24 hours. The mean elimination half-life (t1/2) was 9.06+/-1.33 hours and area under the serum concentration vs time curve (AUC) was 20.54+/-1.70 mg h/L. Highest mean peritoneal fluid concentration was 2.15+/-0.49 microg/mL at 2 hours. Highest mean synovial fluid concentration was 1.17+/-0.28 microg/mL at 4 hours. Highest mean urine concentration was 536.67+/-244.79 microg/mL at 2 hours. Highest mean endometrial concentration was 0.72+/-0.23 microg/g at 1.5 hours. Mean CSF concentration was 0.46+/-0.55 microg/mL at 3 hours. The minimum inhibitory concentration of orbifloxacin required to inhibit 90% of isolates (MIC90) ranged from < or = 0.12 to > 8.0 microg/mL, with gram-negative organisms being more sensitive than gram-positive organisms. Orbifloxacin was uniformly absorbed in the 6 mares and was well distributed into body fluids and endometrial tissue. At a dosage of 7.5 mg/kg once a day, many gram-negative pathogens, such as Actinobacillus equuli, Escherichia coli, Pasteurella spp., and Salmonella spp. would be expected to be susceptible to orbifloxacin.  相似文献   

7.
Enrofloxacin and marbofloxacin were administered to six healthy dogs in separate crossover experiments as a single oral dose (5 mg/kg) and as a constant rate IV infusion (1.24 and 0.12 mg/h.kg, respectively) following a loading dose (4.47 and 2 mg/kg, respectively) to achieve a steady-state concentration of approximately 1 microg/mL for 8 h. Interstitial fluid (ISF) was collected with an in vivo ultrafiltration device at the same time period as plasma to measure protein unbound drug concentrations at the tissue site and assess the dynamics of drug distribution. Plasma and ISF were analyzed for enrofloxacin, its active metabolite ciprofloxacin, and for marbofloxacin by high performance liquid chromatography (HPLC). Lipophilicity and protein binding of enrofloxacin were higher than for marbofloxacin and ciprofloxacin. Compared to enrofloxacin, marbofloxacin had a longer half-life, higher Cmax, and larger AUC(0-infinity) in plasma and ISF after oral administration. Establishing steady state allowed an assessment of the dynamics of drug concentrations between plasma and ISF. The ISF and plasma-unbound concentrations were similar during the steady-state period despite differences in lipophilicity and pharmacokinetic parameters of the drugs.  相似文献   

8.
The purpose of this study was to establish the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in the plasma and interstitial fluid (ISF) following subcutaneous (s.c.) administration of enrofloxacin. Ultrafiltration probes were placed in the s.c. tissue, gluteal musculature, and pleural space of five calves. Each calf received 12.5 mg/kg of enrofloxacin. Plasma and ISF samples were collected for 48 h after drug administration and analyzed by high pressure liquid chromatography. Plasma protein binding of enrofloxacin and ciprofloxacin was measured using a microcentrifugation system. Tissue probes were well tolerated and reliably produced fluid from each site. The mean +/- SD plasma half-life was 6.8 +/- 1.2 and 7.3 +/- 1 h for enrofloxacin and ciprofloxacin, respectively. The combined (ciprofloxacin + enrofloxacin) peak plasma concentration (Cmax) was 1.52 microg/mL, and the combined area under the curve (AUC) was 25.33 microg/mL. The plasma free drug concentrations were 54% and 81% for enrofloxacin and ciprofloxacin, respectively, and free drug concentration in the tissue fluid was higher than in plasma. We concluded that Cmax/MIC and AUC/MIC ratios for free drug concentrations in plasma and ISF would meet suggested ratios for a targeted MIC of 0.06 microg/mL.  相似文献   

9.
Enrofloxacin pharmacokinetics were studied in European cuttlefish, Sepia officinalis, after a single 5 mg/kg i.v. injection or a 2.5 mg/L 5 h bath. A pilot study with two animals was also performed following a 10 mg/kg p.o. administration. The concentration of enrofloxacin in hemolymph was assayed using high-performance liquid chromatography (HPLC) and pharmacokinetic parameters were derived from compartmental methods. In the i.v. study, the terminal half-life (t(1/2)), apparent volume of distribution, and systemic clearance were respectively 1.81 h, 385 mL/kg, and 4.71 mL/min/kg. Following bath administration the t(1/2), peak hemolymph concentration (C(max)), and area under the curve to infinity (AUC(0-infinity)) were 1.01 h, 0.5 +/- 0.12 mug/mL, and 0.98 microg.h/mL, respectively. After oral administration, the t(1/2), C(max), and AUC(0-infinity) were 1.01 h, 10.95 microg/mL, 26.71 mug.h/mL, respectively. The active metabolite of enrofloxacin, ciprofloxacin, was not detected in any samples tested. The hemolymph concentration was still above minimum inhibitory concentration (MIC) values for shrimp and fish bacterial isolates at 6 h after i.v. administration, therefore, a dose of 5 mg/kg i.v. every 8-12 h is suggested for additional studies of efficacy. The C(max) value for the water bath was lower than for the i.v. study, but a bath of 2.5 mg/L for 5 h once to twice daily is suggested for additional studies to test efficacy against highly susceptible organisms. Although only two animals were used for the oral study, a dose of 10 mg/kg produced hemolymph concentrations of enrofloxacin that were in a range consistent with therapeutic efficacy in other species.  相似文献   

10.
The pharmacokinetics of enrofloxacin (EFL) and its active metabolite ciprofloxacin (CIP) was investigated in 7-8 month old turkeys (6 birds per sex). EFL was administered intravenously (i.v.) and orally (p.o.) at a dose 10 mg kg(-1) body weight. Blood was taken prior to and at 0.17, 0.33, 0.5, 1, 2, 3, 4, 6, 8, 10 and 24 h following drug administration. The concentrations of EFL and CIP in blood serum were determined by high-performance liquid chromatography (HPLC). Serum concentrations versus time were analysed by a noncompartmental analysis. The elimination half-live and the mean residence time of EFL after i.v. injection for the serum were after oral administration 6.64+/-0.90 h, 8.96+/-1.18 h and 6.92+/-0.97 h, 11.91+/-1.87 h, respectively. After single p.o. administration, EFL was absorbed slowly (MAT=2.76+/-0.48 h) with time to reach maximum serum concentrations of 6.33+/-2.54 h. Maximum serum concentrations was 1.23+/-0.30 microg mL(-1). Oral bioavailability for for EFL after oral administration was found to be 69.20+/-1.49%. The ratios C(max)/MIC and AUC(0 --> 24)/MIC were respectively from 161.23+/-5.9 h to 12.90+/-0.5 h for the pharmacodynamic predictor C(max)/MIC, and from 2153.44+/-66.6 h to 137.82+/-4.27 h for AUC(0 --> 24)/MIC, for the different clinically significant microorganisms, whose values for MIC varies from 0.008 microg L(-1) to 0.125 microg mL(-1).  相似文献   

11.
This study reports on the administration of a single dose of marbofloxacin (2 mg/kg) to five adult Eurasian buzzards (Buteo buteo) by the intraosseous (IO) route, which has been proposed as a rapid and efficient means for the parenteral delivery of antimicrobial drugs. The drug was rapidly absorbed. Peak marbofloxacin concentration (C(max)) in plasma and area under the concentration-time curve (AUC) of 1.92+/-0.78 microg/mL and 8.53+/-2.73 microg h/mL, respectively. The time marbofloxacin remained in the plasma after IO administration was relatively short (elimination half-life, t(1/2beta)=4.91+/-0.65 h; mean residence time (MRT)=5.38+/-0.57 h). Single dose marbofloxacin gave values for C(max)/minimum inhibitory concentration (MIC) of 19.2 and an AUC/MIC value of 85.3h after IO administration. The IO route appears to be practical and effective for the rapid delivery of marbofloxacin to buzzards.  相似文献   

12.
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.  相似文献   

13.
In a four-period, cross-over study, the fluoroquinolone antibacterial drug marbofloxacin (MB) was administered to calves, alone and in combination with the nonsteroidal anti-inflammatory drug tolfenamic acid (TA). Both drugs were administered intramuscularly (IM) at doses of 2 mg/kg. A tissue cage model of inflammation, based on the actions of the mild irritant carrageenan, was used to evaluate the pharmacokinetics (PK) of MB and MB in combination with TA. MB mean values of area under concentration-time curve (AUC) were 15.1 μg·h/mL for serum, 12.1 μg·h/mL for inflamed tissue cage fluid (exudate) and 9.6 μg·h/mL for noninflamed tissue cage fluid (transudate). Values of C(max) were 1.84, 0.35 and 0.31 μg/mL, respectively, for serum, exudate and transudate. Mean residence time (MRT) of 23.6 h (exudate) and 22.6 h (transudate) also differed significantly from serum MRT (8.6 h). Co-administration of TA did not affect the PK profile of MB. The pharmacodynamics of MB was investigated using a bovine strain of Mannheimia haemolytica. Time-kill curves were established ex vivo on serum, exudate and transudate samples. Modelling the ex vivo serum time-kill data to the sigmoid E(max) equation provided AUC(24 h) /MIC values required for bacteriostatic (18.3 h) and bactericidal actions (92 h) of MB and for virtual eradication of the organism was 139 h. Corresponding values for MB + TA were 20.1, 69 and 106 h. These data were used to predict once daily dosage schedules for a bactericidal action, assuming a MIC(90) value of 0.24 μg/mL, a dose of 2.6 mg/kg for MB and 2.19 mg/kg for MB + TA were determined, which are similar to the currently recommended dose of 2.0 mg/kg.  相似文献   

14.
The pharmacokinetic behaviour of enrofloxacin in greater rheas was investigated after intramuscular (IM) administration of 15 mg/kg. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by high performance liquid chromatography. Enrofloxacin peak plasma concentration (C(max)=3.30+/-0.90 microg/mL) was reached at 24.17+/-9.17 min. The terminal half-life (t(1/2lambda)) and area under the curve (AUC) were 2.85+/-0.54 h and 4.18+/-0.69 microg h/mL, respectively. The AUC and C(max) for ciprofloxacin were 0.25+/-0.06 microg/mL and 0.66+/-0.16 microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, an IM dose of 15 mg/kg of enrofloxacin would appear to be adequate for treating infections caused by highly susceptible bacteria (MIC(90)<0.03 microg/mL) in greater rheas.  相似文献   

15.
The objective of this study was to investigate the pharmacokinetics of marbofloxacin (MAR) following intravenous (iv) and intramuscular (im) administration of a 2.0 mg/kg body weight dosage to five healthy Egyptian buffalo steers. A cross-over design was used with a washout period of 2 weeks. Blood samples were obtained at 0, 5,10,15, and 20 min and at 0.5,0.75,1,2,4,6,8,10,12,24,30 and 48 hours after marbofloxacin administration.The serum marbofloxacin concentrations were quantitated using a modified agar diffusion bioassay method. Marbofloxacin exhibited a relatively high volume of distribution at steady-state (Vdss = 1.77 Lkg), which suggests good tissue penetration, and a total body clearance (Cltot) of 0.18 L/kgxh,which is associated with a long elimination half-life (tl/2beta = 7.52 h). Marbofloxacin was rapidly absorbed at a dosage of 2.0 mg/kg after im administration with an observed maximum serum concentration (Cmax) value of 2.004 microg/mL obtained at a time to peak concentration (tmax) of 0.5 h, and an absolute bioavailability (F %) of 86.79 +/- 5.53 %.The protein-binding ranged from 22 to 24.6 % with an average of 23.4 %. In conclusion, single iv and im administered doses of marbofloxacin were well tolerated by Egyptian buffalo steers. A dosage of 2 mg/kg body weight might not be enough to treat infections caused by bacteria with minimum inhibitory concentration (MIC) at or above 0.2 microg/mL, based on the calculated area under the inhibitory concentration (AUIC).  相似文献   

16.
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.  相似文献   

17.
OBJECTIVE: To determine the pharmacokinetics of marbofloxacin after single IV and orally administered doses in blue and gold macaws. ANIMALS: 10 healthy blue and gold macaws. PROCEDURES: In a crossover study, marbofloxacin (2.5 mg/kg) was administered orally (via crop gavage) to 5 birds and IV to 5 birds. Blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after marbofloxacin administration. After a 4-week washout period, the study was repeated, with the first 5 birds receiving the dose IV and the second 5 birds receiving the dose orally. Serum marbofloxacin concentrations were quantitated by use of a validated liquid chromatography-mass spectrometry assay. RESULTS: After oral administration, mean +/- SD area under the curve was 7.94 +/- 2.08 microg.h/mL, maximum plasma concentration was 1.08 +/- 0.316 microg/mL, and bioavailability was 90.0 +/- 31%. After IV administration of marbofloxacin, the apparent volume of distribution was 1.3 +/- 0.32 L/kg, plasma clearance was 0.29 +/- 0.078 L/h/kg, area under the curve was 9.41 +/- 2.84 microg.h/mL, and the harmonic mean terminal half-life was 4.3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Single IV and orally administered doses of marbofloxacin were well tolerated by blue and gold macaws. The orally administered dose was well absorbed. Administration of marbofloxacin at a dosage of 2.5 mg/kg, PO, every 24 hours may be appropriate to control bacterial infections susceptible to marbofloxacin in this species.  相似文献   

18.
The pharmacokinetics of marbofloxacin were investigated in healthy (n=8) and Mannheimia haemolytica naturally infected (n=8) Simmental ruminant calves following intravenous (i.v.) and intramuscular (i.m.) administration of 2 mg kg(-1) body weight. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography with ultraviolet detection. Following i.v. administration of the drug, the elimination half-life (t(1/2 beta)) and mean residence time (MRT) were significantly longer in diseased calves (8.2h; 11.13 h) than in healthy ones (4.6 h; 6.1 h), respectively. The value of total body clearance (CL(B)) was larger in healthy calves (3 ml min(-1) kg(-1)) than in diseased ones (1.3 ml min(-1) kg(-1)). After single intramuscular (i.m.) administration of the drug, the elimination half-life, mean residence time (MRT) and maximum plasma concentration (C(max)) were higher in diseased calves (8.0, 12 h, 2.32 microg ml(-1)) than in healthy ones (4.7, 7.4 h, 1.4 microg ml(-1)), respectively. The plasma concentrations and AUC following administration of the drug by both routes were significantly higher in diseased calves than in healthy ones. Protein binding of Marbofloxacin was not significantly different in healthy and diseased calves. The mean value for MIC of marbofloxacin for M. haemolytica was 0.1+/-0.06 microg ml(-1). The C(max)/MIC and AUC(24)/MIC ratios were significantly higher in diseased calves (13.0-64.4 and 125-618 h) than in healthy calves (8-38.33 and 66.34-328 h). The obtained results for surrogate markers of antimicrobial activity (C(max)/MIC, AUC/MIC and T > or = MIC) indicate the excellent pharmacodynamic characteristics of the drug in diseased calves with M. haemolytica, which can be expected to optimize the clinical efficacy and minimize the development of resistance.  相似文献   

19.
The pharmacokinetics and pharmacodynamics of orbifloxacin were studied in six clinically healthy Hanwoo cows after intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 3 mg/kg. Orbifloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution and clearance of orbifloxacin after i.v. administration were 0.92 L/kg and 0.24 L/h·kg, respectively. Following i.m. administration, a slow and complete absorption with absolute bioavailability of 101.4%, and a maximum concentration ( C max) of 1.17 μg/mL at 1.04 h were observed. The in vitro serum protein binding was 14.76%. The in vitro antibacterial activity of orbifloxacin against a pathogenic strain of Mannheimia haemolytica ( M. haemolytica ), Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ) was determined . The ex vivo activity of orbifloxacin against M. haemolytica strain was also determined , and these data were integrated with the ex vivo bacterial counts to establish AUC 24h/ MIC values producing bacteriostatic action, bactericidal action and elimination of bacteria. Mean values were 32.7, 51.6 and 102.6 h, respectively. From these data, we predict that orbifloxacin, when administered i.m. at a dosage of 2.5–5 mg/kg once a day, would be effective against bovine pathogens, such as M. haemolytica. Additional studies may be needed to confirm its efficacy in a clinical setting, and to evaluate the penetration of the drug in diseased tissues.  相似文献   

20.
Mammary glands taken at slaughter from healthy lactating cows were perfused in vitro with warmed and gassed Tyrode solution. Marbofloxacin was administered "systemically" via the perfusion fluid at concentrations similar to those measured in plasma following intravenous administration of 2mg/kg marbofloxacin. Samples from the perfusate were taken over a 24h period. Glandular tissue samples at different vertical distances from the teat up to the udder base were gathered from each of the four quarters after 3, 6, 12 and 24h. The marbofloxacin content of the tissue samples was analysed by high performance liquid chromatography with UV detection. The addition of marbofloxacin to the perfusion fluid produced median concentrations above the MIC90 (0.016microg/mL) against Escherichia coli at all glandular tissue sites measured after 3 and 6h with remarkable variations. Samples taken after 12 and 24h contained marbofloxacin in concentrations (median) of 0.22 (<0.05-0.32)microg/g and 0.13 (<0.05-0.16)microg/g. It is concluded that a systemic administration of marbofloxacin is well suited for the treatment of E. coli mastitis.  相似文献   

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