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1.
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   

2.
OBJECTIVE: To evaluate, by use of population pharmacokinetics, the disposition of marbofloxacin in the aqueous humor after IV administration in dogs and identify its potential usefulness in the prophylaxis and treatment of intraocular infection. ANIMALS: 63 dogs. METHODS: Dogs received a single dose of marbofloxacin (2 mg x kg(-1), IV) at various time intervals before cataract surgery. Aqueous humor and blood samples were collected at the beginning of surgery. Marbofloxacin concentrations were measured by high-pressure liquid chromatography. Data were analyzed with a nonlinear mixed-effect model and, by use of population pharmacokinetic parameters, the time course of aqueous humor concentration was simulated for single doses of 3, 4, and 5.5 mg x kg(-1) IV. Pharmacodynamic surrogate markers and measured aqueous humor concentrations were used to predict in vivo antimicrobial activity. RESULTS: A maximum marbofloxacin concentration of 0.41 +/- 0.17 microg x mL(-1) was reached in the aqueous humor 3.5 hours after IV administration. In the post-distributive phase, marbofloxacin disappeared from aqueous humor with a half-life of 780 minutes. The percentage penetration into the aqueous humor was 38%. Predictors of antimicrobial effects of marbofloxacin (2 mg x kg(-1), IV) indicated that growth of the enterobacteriaceae and certain staphylococcal species would be inhibited in the aqueous humor. Marbofloxacin administered IV at a dose of 5.5 mg x kg(-1) would be predicted to inhibit growth of Pseudomonas aeruginosa and all strains of staphylococci but would not eradicate streptococcal infections. CONCLUSIONS AND CLINICAL RELEVANCE: Marbofloxacin administered IV can penetrate the aqueous humor of canine eyes and may be suitable for prophylaxis or treatment of certain anterior chamber infections.  相似文献   

3.
The purpose of this study was to determine the concentration of enrofloxacin and its active metabolite, ciprofloxacin, in alveolar macrophages (AM) and epithelial lining fluid (ELF) of the lungs in comparison to plasma concentrations in healthy dogs. Eleven dogs were given a single oral dose (5 mg/kg) of enrofloxacin. Four hours later, plasma and bronchoalveolar lavage (BAL) fluid were collected. Cells were separated from the BAL fluid and lysed for determination of drug concentrations within AM. Supernatant was used to determine concentrations of drugs in ELF. Drug assays were performed by high-performance liquid chromatography.
  The concentration of enrofloxacin (mean ± SD) was 0.33 ± 0.14 μg/mL in plasma, 3.34 ± 2.4 μg/mL in AM and 4.79 ± 5.0 μg/mL in ELF. The concentration of ciprofloxacin was 0.42 ± 0.26 μg/mL in plasma, 1.15 ± 1.03 μg/mL in AM and 0.26 ± 0.26 μg/mL in ELF. Mean concentrations of both drugs in AM were greater than in plasma (AM to plasma ratio, 10.3 for enrofloxacin and 4.7 for ciprofloxacin). Mean concentrations of enrofloxacin, but not ciprofloxacin, in ELF were greater than in plasma (ELF to plasma ratio, 13.5 for enrofloxacin and 0.52 for ciprofloxacin). Enrofloxacin concentrations in AM and ELF largely exceeded the MICs of the major bacterial pathogens and surpassed by about two times the breakpoint MIC of that drug, and ciprofloxacin concentrations in AM surpassed the MIC of many susceptible organisms. These results suggest that sufficient antimicrobial activity is present in AM and ELF of dogs following oral administration of enrofloxacin to be effective in the treatment of lower respiratory tract infections involving susceptible organisms.  相似文献   

4.
OBJECTIVE: To compare penetration of IV administered marbofloxacin in intraocular fluids of healthy and inflamed eyes in rabbits with endotoxin-induced endophthalmitis. ANIMALS: 35 pigmented rabbits. PROCEDURES: Endophthalmitis was induced in the right eye via intravitreal administration of Escherichia coli endotoxin. The left eye was a control eye. After 24 hours, a single dose of marbofloxacin (4 mg/kg, IV) was administered. Groups of rabbits (n = 5/group) were euthanized 0.5, 1, 2, 4, 6, 10, and 18 hours later, and blood and ocular fluids were collected. Marbofloxacin concentrations were determined via reverse-phase high-performance liquid chromatography, and pharmacokinetic analysis of the data was performed with a mono-compartmental model. RESULTS: Mean area under the aqueous concentration-time curve was significantly lower in control eyes (1.64 +/- 0.07 microg*h/mL) than in inflamed eyes (3.31 +/- 0.11 microg*h/mL). Similarly, drug penetration into aqueous humor was 33% and 65% for control eyes and inflamed eyes, respectively. Mean area under the vitreous humor concentration-time curve for control eyes(1.75 +/- 0.05 microg*h/mL) was significantly less than for inflamed eyes (2.39 +/- 0.16 microg*h/mL). In the vitreous humor, corresponding penetrations were 34% and 47%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Penetration of marbofloxacin into the aqueous and vitreous humor after IV administration was significantly enhanced by intraocular inflammation, suggesting a role for this antimicrobial in the prophylaxis or treatment of bacterial endophthalmitis caused by susceptible pathogens.  相似文献   

5.
The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose subcutaneous (SC) administration of 2mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography and the data obtained were subjected to non-compartmental kinetic analysis. Marbofloxacin peak plasma concentration (C(max)=1.77+/-0.24microg/mL) was reached 1.25+/-0.50h (T(max)) after SC administration. The elimination half-life (t(1/2beta)) and area under curve (AUC) were 5.74+/-1.21h and 8.15 vs 2.33microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, it was concluded that a SC dose of 2mg/kg/24h of marbofloxacin could be adequate to treat infections caused by high susceptible bacteria like Escherichia coli or Salmonella spp.  相似文献   

6.
Pharmacokinetics of marbofloxacin in horses   总被引：3，自引：0，他引：3  
Marbofloxacin is a fluoroquinolone antibiotic expected to be effective in the treatment of infections involving gram-negative and some gram-positive bacteria in horses. In order to design a rational dosage regimen for the substance in horses, the pharmacokinetic properties of marbofloxacin were investigated in 6 horses after i.v., subcutaneous and oral administration of a single dose of 2 mg/kg bwt and the minimal inhibitory concentrations (MIC) assessed for bacteria isolated from equine infectious pathologies. The clearance of marbofloxacin was mean +/- s.d. 0.25 +/- 0.05 l/kg/h and the terminal half-life 756 +/- 1.99 h. The marbofloxacin absolute bioavailabilities after subcutaneous and oral administration were 98 +/- 11% and 62 +/- 8%, respectively. The MIC required to inhibit 90% of isolates (MIC90) was 0.027 microg/ml for enterobacteriaceae and 0.21 microg/ml for Staphylococcus aureus. The values of surrogate markers of antimicrobial efficacy (AUIC, Cmax/MIC ratio, time above MIC90) were calculated and the marbofloxacin concentration profiles simulated for repeated administrations. These data were used to determine rational dosage regimens for target bacteria. Considering the breakpoint values of efficacy indices for fluoroquinolones, a marbofloxacin dosage regimen of 2 mg/kg bwt/24 h by i.v., subcutaneous or oral routes was more appropriate for enterobacteriaceae than for S. aureus.  相似文献   

7.
The pharmacokinetics of marbofloxacin was investigated after intravenous (IV) and intramuscular (IM) administration, both at a dose rate of 5 mg/kg BW, in six clinically healthy domestic ostriches. Plasma concentrations of marbofloxacin was determined by a HPLC/UV method. The high volume of distribution (3.22+/-0.98 L/kg) suggests good tissue penetration. Marbofloxacin presented a high clearance value (2.19+/-0.27 L/kgh), explaining the low AUC values (2.32+/-0.30 microgh/mL and 2.25+/-0.70 microgh/mL, after IV and IM administration, respectively) and a short half life and mean residence time (t(1/2 beta)=1.47+/-0.31 h and 1.96+/-0.35 h; MRT=1.46+/-0.02 h and 2.11+/-0.30 h, IV and IM, respectively). The absorption of marbofloxacin after IM administration was rapid and complete (C(max)=1.13+/-0.29 microg/mL; T(max)=0.36+/-0.071 h; MAT=0.66+/-0.22 h and F (%)=95.03+/-16.89).  相似文献   

8.
OBJECTIVE: To study the hemodynamic effects of marbofloxacin (MBF) in isoflurane-anesthetized dogs. ANIMALS: 6 healthy 8-month-old Beagles. PROCEDURE: Anesthesia was induced with sodium thiopental and maintained with isoflurane. Cardiovascular variables were monitored throughout anesthesia. Marbofloxacin was administered by an IV bolus at 2 mg/kg, followed 10 minutes later by an infusion at a rate of 40 mg/kg/h for 30 minutes (total dose, 20 mg/kg). Plasma MBF concentrations were measured by high-performance liquid chromatography. RESULTS: The mean peak concentration during MBF infusion was 34.2 +/- 6.4 microg/mL. The IV administration of the MBF bolus did not alter any cardiovascular variable in isoflurane-anesthetized dogs. Significant changes were found during infusion when a cumulative dose of 12 mg/kg had been given. The maximal decreases observed at the end of the infusion were 16% in heart rate, 26% in systolic left ventricular pressure, 33% in systolic aortic pressure, 38% in diastolic aortic pressure, 29% in cardiac output, and 12% in QT interval. All dogs recovered rapidly from anesthesia at the end of the experiment. CONCLUSIONS AND CLINICAL RELEVANCE: MBF may safely be used at 2 mg/kg IV in isoflurane-anesthetized dogs, and significant adverse cardiovascular effects are found only when 6 to 8 times the recommended dose is given.  相似文献   

9.
OBJECTIVE: To estimate pharmacokinetic variables and measure tissue fluid concentrations of meropenem after IV and SC administration in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURE: Dogs were administered a single dose of meropenem (20 mg/kg) IV and SC in a crossover design. To characterize the distribution of meropenem in dogs and to evaluate a unique tissue fluid collection method, an in vivo ultrafiltration device was used to collect interstitial fluid. Plasma, tissue fluid, and urine samples were analyzed by use of high-performance liquid chromatography. Protein binding was determined by use of an ultrafiltration device. RESULTS: Plasma data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean +/- SD values for half-life, volume of distribution, and clearance after IV administration for plasma samples were 0.67 +/- 0.07 hours, 0.372 +/- 0.053 L/kg, and 6.53 +/- 1.51 mL/min/kg, respectively, and half-life for tissue fluid samples was 1.15 +/- 0.57 hours. Half-life after SC administration was 0.98 +/- 0.21 and 1.31 +/- 0.54 hours for plasma and tissue fluid, respectively. Protein binding was 11.87%, and bioavailability after SC administration was 84%. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of our data revealed that tissue fluid and plasma (unbound fraction) concentrations were similar. Because of the kinetic similarity of meropenem in the extravascular and vascular spaces, tissue fluid concentrations can be predicted from plasma concentrations. We concluded that a dosage of 8 mg/kg, SC, every 12 hours would achieve adequate tissue fluid and urine concentrations for susceptible bacteria with a minimum inhibitory concentration of 0.12 microg/mL.  相似文献   

10.
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   

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.
The pharmacokinetic properties of marbofloxacin, a third generation fluoroquinolone, were investigated in six cats after single intravenous (IV) and repeat oral (PO) administration at a daily dose of 2 mg/kg. Marbofloxacin serum concentration was analysed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as micro-organism test. Serum marbofloxacin disposition was best described by bicompartmental and mono-compartmental open models with first-order elimination after IV and oral dosing respectively. After IV administration, distribution was rapid (T(1/2(d)) 0.23+/-0.24 h) and wide, as reflected by the steady-state volume of distribution of 1.01+/-0.15 L/kg. Elimination from the body was slow with a body clearance of 0.09+/-0.02 L/h kg and a T(1/2) of 7.98+/-0.57 h. After repeat oral administration, absorption half-life was 0.86+/-1.59 h and T(max) of 1.94+/-2.11 h. Bioavailability was almost complete (99+/-29%) with a peak plasma concentration at the steady-state of 1.97+/-0.61 mug/mL. Drug accumulation was not significant after six oral administrations. Calculation of efficacy predictors showed that marbofloxacin has good therapeutic profile against Gram-negative and Gram-positive bacteria with a MIC(50) value <0.25 microg/mL.  相似文献   

13.
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   

14.
The pharmacokinetic properties of marbofoxacin, a third generation fluoroquinolone, were investigated in 12 healthy adult cats after single subcutaneous (SC) administration of 2 mg/kg BW (Part I, n=8 cats) and 4 mg/kg BW (Part II, n=4 cats). In each part of the study blood and urine samples were collected before treatment and thereafter for 5 days. The plasma and urine concentrations of marbofloxacin were determined by HPLC with UV detection. Pharmacokinetic calculations were performed for each treated animal using an open one-compartment-model with first-order elimination after SC dosing. Marbofloxacin in plasma (means): Maximum concentrations (Cmax) of about 1.2 and 3.0 microg/ml were measured 2.3 and 4 hours (tmax) after dosing of 2 and 4 mg/kg BW, respectively. Elimination from the body was low with a total clearance (Cl/F) of approximately 0.1 l/h/kg for both dosages. The half-life (t 1/2) for this process was calculated with 8-10 hours. AUC increased almost proportional when doubling the dose, i.e., 19.77 +/- 6.25 microg * h/ml (2 mg/kg BW) and 51.26 +/- 11.83 microg * h/ml (4 mg/kg BW). Plasma kinetics measured were in accordance with data from literature. Marbofloxacin in urine (means): Maximum drug concentrations were detected 4 and 8 hours after dosing with 70 microg/ml (2 mg/kg BW) and 160 microg/ml (4 mg/kg BW), respectively. Inhibitory effects of the urinary matrix on the antimicrobial activity of the drug were taken into account when performing PK/PD calculations. However, a concentration-dependent bactericidal activity (Cmax/MIC > 8-10) which is claimed for fluoroquinolones was sufficiently met with focus on Escherichia (E.) coli (MIC90 0.5 microg/ml). In the same matrix a threshold value of 1.0 microg/ml was undercut 82 and 116 hours after SC dosing, respectively. Hence, a time-dependent bacteria killing kinetic (T > MIC) which may be of relevance for some Gram-positive germs like Staphylococcus spp. (MIC90 1.0 microg/ml) should be covered, too.  相似文献   

15.
OBJECTIVE: To determine the effect of 6 plasma ketamine concentrations on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS: 6 dogs. PROCEDURE: In experiment 1, the MAC of isoflurane was measured in each dog and the pharmacokinetics of ketamine were determined in isoflurane-anesthetized dogs after IV administration of a bolus (3 mg/kg) of ketamine. In experiment 2, the same dogs were anesthetized with isoflurane in oxygen. A target-controlled IV infusion device was used to administer ketamine and to achieve plasma ketamine concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL by use of parameters obtained from experiment 1. The MAC of isoflurane was determined at each plasma ketamine concentration, and blood samples were collected for ketamine and norketamine concentration determination. RESULTS: Actual mean +/- SD plasma ketamine concentrations were 1.07 +/- 0.42 microg/mL, 1.62 +/- 0.98 microg/mL, 3.32 +/- 0.59 microg/mL, 4.92 +/- 2.64 microg/mL, 13.03 +/- 10.49 microg/mL, and 22.80 +/- 25.56 microg/mL for target plasma concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL, respectively. At these plasma concentrations, isoflurane MAC was reduced by 10.89% to 39.48%, 26.77% to 43.74%, 25.24% to 84.89%, 44.34% to 78.16%, 69.62% to 92.31%, and 71.97% to 95.42%, respectively. The reduction in isoflurane MAC was significant, and the response had a linear and quadratic component. Salivation, regurgitation, mydriasis, increased body temperature, and spontaneous movements were some of the adverse effects associated with the high plasma ketamine concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine appears to have a potential role for balanced anesthesia in dogs.  相似文献   

16.
OBJECTIVE: To determine the pharmacokinetics of marbofloxacin after oral administration in juvenile harbor seals (Phoca vitulina) at a dose of 5 mg/kg (2.3 mg/lb) and to compare pharmacokinetic variables after pharmacokinetic analysis by na?ve averaged, na?ve pooled, and nonlinear mixed-effects modeling. DESIGN: Original study. Animals-33 male and 22 female juvenile seals being treated for various conditions. PROCEDURES: Blood collection was limited to < or = 3 samples/seal. Plasma marbofloxacin concentrations were measured via high-pressure liquid chromatography with UV detection. RESULTS: Mean +/- SE dose of marbofloxacin administered was 5.3 +/- 0.1 mg/kg (2.4 +/- 0.05 mg/lb). The terminal half-life, volume of distribution (per bioavailability), and clearance (per bioavailability) were approximately 5 hours, approximately 1.4 L/kg, and approximately 3 mL/min/kg, respectively (values varied slightly with the method of calculation). Maximum plasma concentration and area under the plasma-time concentration curve were approximately 3 microg/mL and 30 h x microg/mL, respectively. Na?ve averaged and na?ve pooled analysis appeared to yield a better fit to the population, but nonlinear mixed-effects modeling yielded a better fit for individual seals. CONCLUSIONS AND CLINICAL RELEVANCE: Values of pharmacokinetic variables were similar regardless of the analytic method used. Pharmacokinetic variability can be assessed with nonlinear mixed-effects modeling, but not with na?ve averaged or na?ve pooled analysis. Visual observation by experienced trainers revealed no adverse effects in treated seals. Plasma concentrations attained with a dosage of 5 mg/kg every 24 hours would be expected to be efficacious for treatment of infections caused by susceptible bacteria (excluding Pseudomonas aeruginosa).  相似文献   

17.
OBJECTIVE: To determine the pharmacokinetics of voriconazole following IV and PO administration and assess the distribution of voriconazole into body fluids following repeated PO administration in horses. ANIMALS: 6 clinically normal adult horses. PROCEDURES: All horses received voriconazole (10 mg/kg) IV and PO (2-week interval between treatments). Plasma voriconazole concentrations were determined prior to and at intervals following administration. Subsequently, voriconazole was administered PO (3 mg/kg) twice daily for 10 days to all horses; plasma, synovial fluid, CSF, urine, and preocular tear film concentrations of voriconazole were then assessed. RESULTS: Mean +/- SD volume of distribution at steady state was 1,604.9 +/- 406.4 mL/kg. Systemic bioavailability of voriconazole following PO administration was 95 +/- 19%; the highest plasma concentration of 6.1 +/- 1.4 microg/mL was attained at 0.6 to 2.3 hours. Mean peak plasma concentration was 2.57 microg/mL, and mean trough plasma concentration was 1.32 microg/mL. Mean plasma, CSF, synovial fluid, urine, and preocular tear film concentrations of voriconazole after long-term PO administration were 5.163 +/- 1.594 microg/mL, 2.508 +/- 1.616 microg/mL, 3.073 +/- 2.093 microg/mL, 4.422 +/- 0.8095 microg/mL, and 3.376 +/- 1.297 microg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole distributed quickly and widely in the body; following a single IV dose, initial plasma concentrations were high with a steady and early decrease in plasma concentration. Absorption of voriconazole after PO administration was excellent, compared with absorption after IV administration. Voriconazole appears to be another option for the treatment of fungal infections in horses.  相似文献   

18.
OBJECTIVES: To determine pharmacokinetic characteristics of marbofloxacin after a single IV and oral administration and tissue residues after serial daily oral administration in chickens. ANIMALS: 40 healthy broiler chickens. PROCEDURE: Two groups of chickens (groups A and B; 8 chickens/group) were administered a single IV and oral administration of marbofloxacin (2 mg/kg). Chickens of group C (n = 24) were given serial daily doses of marbofloxacin (2 mg/kg, PO, q 24 h for 3 days). Plasma (groups A and B) and tissue concentrations (group C) of marbofloxacin and its major metabolite N-desmethyl-marbofloxacin were determined by use of high-performance liquid chromatography. Residues of marbofloxacin and N-desmethylmarbofloxacin were measured in target tissues. RESULTS: Elimination half-life and mean residence time of marbofloxacin in plasma were 5.26 and 4.36 hours after IV administration and 8.69 and 8.55 hours after oral administration, respectively. Maximal plasma concentration was 1.05 microg/ml, and interval from oral administration until maximum concentration was 1.48 hours. Oral bioavailability of marbofloxacin was 56.82%. High concentrations of marbofloxacin and N-desmethyl-marbofloxacin were found in the kidneys, liver, muscles, and skin plus fat 24 hours after the final dose of marbofloxacin; however, marbofloxacin and N-desmethyl-marbofloxacin were detected in only hepatic (27.6 and 98.7 microg/kg, respectively) and renal (39.7 and 69.1 microg/kg, respectively) tissues 72 hours after termination of marbofloxacin treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of pharmacokinetic data obtained in this study reveals that a minimal therapeutic dose of 2 mg/kg, PO, every 24 hours should be appropriate for control of most infections in chickens.  相似文献   

19.
The pharmacokinetic behaviour of marbofloxacin, a new fluoroquinolone antimicrobial agent developed exclusively for veterinary use, was studied in mature horses (n = 5) after single-dose i.v. and i.m. administrations of 2 mg/kg bwt. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and data obtained were subjected to compartmental and noncompartmental kinetic analysis. This compound presents a relatively high volume of distribution (V(SS) = 1.17 +/- 0.18 l/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.19 +/- 0.042 l/kgh, which is related to a long elimination half-life (t(1/2beta) = 4.74 +/- 0.8 h and 5.47 +/- 1.33 h i.v. and i.m. respectively). Marbofloxacin was rapidly absorbed after i.m. administration (MAT = 33.8 +/- 14.2 min) and presented high bioavailability (F = 87.9 +/- 6.0%). Pharmacokinetic parameters are not significantly different between both routes of administration (P>0.05). After marbofloxacin i.m. administration, no adverse reactions at the site of injection were observed. Serum CK activity levels 12 h after administration increased over 8-fold (range 3-15) compared with pre-injection levels, but this activity decreased to 3-fold during the 24 h follow-up period. Based on the value of surrogate markers to predict clinical success, Cmax/MIC ratio or AUC/MIC ratio, single daily marbofloxacin dose of 2 mg/kg bwt may not be effective in treating infections in horses caused by pathogens with an MIC > or = 0.25 microg/ml. However, if we use a classical antimicrobial efficacy criteria, marbofloxacin can reach a high plasma peak concentration and maintain concentrations higher than MICs determined for marbofloxacin against most gram-negative veterinary pathogens throughout the administration period. Taking into account the fact that fluoroquinolones are considered to have a concentration-dependent effect and a long postantibiotic effect against gram-negative bacteria, a dose of 2 mg/kg bwt every 24 h could be adequate for marbofloxacin in horses.  相似文献   

20.
OBJECTIVES: To measure serum polymyxin B concentration after single and repeated IV infusions in horses. ANIMALS: 5 healthy horses. PROCEDURES: In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-alpha. Urine was collected prior to the first drug infusion and 24 hours after the fifth drug infusion for determination of urinary gamma-glutamyl transferase (GGT)-to-creatinine ratios. RESULTS: In study 1, mean +/- SEM maximal serum polymyxin B concentration was 2.93 +/- 0.38 microg/mL. Polymyxin B was undetectable 18 hours after infusion. In study 2, maximal polymyxin B concentrations after the first and fifth doses were 2.98 +/- 0.81 microg/mL and 1.91 +/- 0.50 microg/mL, respectively. Mean trough concentration for all doses was 0.22 +/- 0.01 microg/mL. A significant effect of repeated administration on peak and trough serum concentration was not detected. Urine GGT-to-creatinine ratios were not affected by polymyxin B administration. CONCLUSIONS AND CLINICAL RELEVANCE: Polymyxin B given as multiple infusions to healthy horses by use of this protocol did not accumulate in the vascular compartment and appeared safe. Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as treatment for endotoxemia.  相似文献   

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