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1.
The pharmacokinetics of florfenicol and its active metabolite florfenicol amine were investigated in rabbits after a single intravenous (i.v.) and oral (p.o.) administration of florfenicol at 20 mg/kg bodyweight. The plasma concentrations of florfenicol and florfenicol amine were determined simultaneously by an LC/MS method. After i.v. injection, the terminal half-life (t(1/2lambdaz)), steady-state volume of distribution, total body clearance and mean residence time of florfenicol were 0.90 +/- 0.20 h, 0.94 +/- 0.19 L/kg, 0.63 +/- 0.06 L/h/kg and 1.50 +/- 0.34 h respectively. The peak concentrations (C(max)) of florfenicol (7.96 +/- 2.75 microg/mL) after p.o. administration were observed at 0.90 +/- 0.38 h. The t(1/2lambdaz) and p.o. bioavailability of florfenicol were 1.42 +/- 0.56 h and 76.23 +/- 12.02% respectively. Florfenicol amine was detected in all rabbits after i.v. and p.o. administration. After i.v. and p.o. administration of florfenicol, the observed Cmax values of florfenicol amine (5.06 +/- 1.79 and 3.38 +/- 0.97 microg/mL) were reached at 0.88 +/- 0.78 and 2.10 +/- 1.08 h respectively. Florfenicol amine was eliminated with an elimination half-life of 1.84 +/- 0.17 and 2.35 +/- 0.94 h after i.v. and p.o. administration respectively.  相似文献   

2.
The pharmacokinetics of florfenicol and its metabolite, florfenicol amine, was investigated after its intravenous (i.v.) and oral (p.o.) administration of 20 mg/kg of body weight in Korean catfish (Silurus asotus). After i.v. florfenicol injection (as a bolus), the terminal half-life (t(1/2)), the volume of distribution at steady state (V(dss)), and total body clearance were 11.12 +/- 1.06 h, 1.09 +/- 0.09 L/kg and 0.07 +/- 0.01 L x kg/h respectively. After p.o. administration of florfenicol, the t(1/2), C(max), t(max) and oral bioavailability (F) were 15.69 +/- 2.59 h, 9.59 +/- 0.36 microg/mL, 8 h and 92.61 +/- 10.1% respectively. Florfenicol amine, an active metabolite of florfenicol, was detected in all fish. After i.v. and p.o. administration of florfenicol, the observed C(max) values of florfenicol amine (3.91 +/- 0.69 and 3.57 +/- 0.65 mg/L) were reached at 0.5 and 7.33 +/- 1.15 h. The mean metabolic rate of florfenicol amine after i.v. and p.o. administration was 0.4 and 0.5 respectively.  相似文献   

3.
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   

4.
Pharmacokinetics of florfenicol in North American elk (Cervus elaphus)   总被引：1，自引：0，他引：1  
Florfenicol pharmacokinetics after administration of a single subcutaneous (s.c.) dose of 40 mg/kg of body weight in adult elk (Cervus elaphus) was investigated. Serum florfenicol concentrations were determined by a sensitive high-performance liquid chromatographic method with limit of quantification of 0.03 microg/mL. Florfenicol pharmacokinetic parameters in elk were estimated using a noncompartmental approach. After a single s.c. injection, florfenicol concentrations remained above 1 microg/mL for approximately 36 h and above 0.5 microg/mL for approximately 72 h. Following s.c. injection, florfenicol was absorbed rapidly with a mean maximum concentration (C(max)) of 3.7 microg/mL achieved at 4.2 h (T(max)). The C(max) value in elk is similar to values reported in cattle at the same dose, suggesting that the 40 mg/kg s.c. dose achieves therapeutic concentrations in elk. A mean elimination half-life (t(1/2)) of 44 h is shorter than that reported in cattle. The more rapid elimination half-life in elk suggests that elk may require a multiple dose regimen for therapeutic success with s.c. Nuflor. We recommend s.c. Nuflor be administered subcutaneously to elk every 24 h at a dose level of 40 mg/kg.  相似文献   

5.
The objective of this study was to evaluate the efficacy of regional intravenous (i.v.) injection of ceftiofur in delivery of this drug to joint fluid and plasma in a limb distal to a tourniquet in five, healthy, adult, mixed breed beef cattle. A tourniquet was positioned in the mid-metacarpal region, and 500 mg of ceftiofur was administered through a catheter in the dorsal common digital vein (DCDV). Plasma samples were collected from the catheter at 15, 30 and 45 min postinjection, and from the abaxial proper palmar vein (APPV) at 15 min postinjection. Synovial fluid was collected from the metacarpal phalangeal joint at 45 min postinjection. Ceftiofur concentrations were estimated in plasma and synovial fluid using high-pressure liquid chromatography (HPLC) and a microbiological assay utilizing Pasteurella haemolytica as the test organism. Both assays indicated highest plasma concentrations of ceftiofur at 15 min, with the concentrations declining with time. Concentrations of ceftiofur in plasma obtained from the DCDV were not significantly different from APPV levels, indicating rapid distribution of ceftiofur within the limb. Microbiological assay always demonstrated higher concentrations of ceftiofur compared with HPLC assay, because the former probably also detected the active metabolites of ceftiofur as well as the parent compound. At 45 min, ceftiofur concentrations determined by HPLC were 251+/-97 and 15+/-5 microg/mL in plasma and synovial fluid, respectively. Regional intravenous injection appears to be a feasible technique to produce rapid distribution of ceftiofur within the limb well above therapeutic concentrations.  相似文献   

6.
OBJECTIVE: To report tissue gentamicin concentrations after intraosseous (IO) perfusion in standing horses. STUDY DESIGN: In vivo study. ANIMALS OR SAMPLE POPULATION: Twelve horses. METHODS: Sedated horses had a cannulated cortical bone screw inserted into the dorsolateral aspect of the treated metacarpus and a tourniquet applied proximally. Gentamicin (2.2 mg/kg) diluted in sterile saline solution (0.1 mL/kg) was infused through the screw. Two horses were euthanatized at each time interval: 0, 2, 6, 12, 24, and 36 hours. Synovial fluid and bone samples were collected distal to the screw from both forelimbs. Gentamicin concentrations were measured using fluorescence polarization immunoassay. RESULTS: The highest synovial fluid gentamicin concentrations were 385+/-273 microg/mL (mean+/-SD) in the metacarpophalangeal joint, 225+/-205 microg/mL in the proximal interphalangeal joint, 215+/-205 microg/mL in the distal interphalangeal joint, 382+/-195 microg/mL in the digital flexor tendon sheath, and 206+/-161 microg/mL in the navicular bursa. The highest bone concentrations of gentamicin were 55+/-30 microg/g in the distal metacarpus, 34+/-27 microg/g in the proximal, 16+/-15 microg/g in the middle, and 16+/-2.2 microg/g in the distal phalanges, and 27+/-17 microg/g in the proximal and 24+/-11 microg/g in the distal sesamoid bones. CONCLUSION: Standing IO perfusion of gentamicin resulted in local antibiotic concentrations in the synovial structures and bones of the distal aspect of the limb that exceed the reported minimum inhibitory concentration of pathogens commonly implicated in equine orthopedic infections. CLINICAL RELEVANCE: Standing IO perfusion of gentamicin in the distal aspect of the limb should be considered for treatment of orthopedic infections of this region in horses.  相似文献   

7.
Pharmacokinetics of florfenicol 30% injectable solution was determined in lactating cows after intravenous, intramammary and intramuscular administration. Serum concentration-time data generated in the present study were analysed by non-compartmental methods based on statistical moment theory. Florfenicol half-life was 176 min, mean residence time 129 min, volume of distribution at steady-state 0.35 L/kg, and total body clearance 2.7 mL/min·kg after intravenous administration at 20 mg/kg. The absorption after intramuscular administration appeared slow and the kinetic parameters and the serum concentration vs. time curve were characteristic of absorption rate-dependent elimination. The absorption after intramammary administration of florfenicol at 20 mg/kg was good (53.9%) and resulted in serum concentrations with apparent clinical significance. The intramammary administration resulted in serum florfenicol concentrations that were significantly higher than the respective serum concentrations following Intravenous administration 4 h after administration and thereafter. Florfenicol absorption was faster from the mammary gland than from the muscle. The maximum serum concentrations ( C max) were 6.9 μg/mL at 360 min after intramammary administration and 2.3 μg/mL at 180 min after intramuscular administration. The bioavailability of florfenicol was 54% and 38% after intramammary and intramuscular administration, respectively. The C max in milk was 5.4 μg/mL at 180 min after intravenous and 1.6 μg/mL at 600 min after intramuscular administration.  相似文献   

8.
A study on bioavailability and pharmacokinetics of florfenicol was conducted in 20 crossbred healthy sheep following a single intravenous (i.v.) and intramuscular (i.m.) doses of 20 and 30 mg/kg body weight (b.w.). Florfenicol concentrations in serum were determined by a validated high-performance liquid chromatography method with UV detection at a wavelength of 223 nm in which serum samples were spiked with chloramphenicol as internal standard. Serum concentration-time data after i.v. administration were best described by a three-compartment open model with values for the distribution half-lives (T(1/2alpha)) 1.51 +/- 0.06 and 1.59 +/- 0.10 h, elimination half-lives (T(1/2beta)) 18.83 +/- 6.76 and 18.71 +/- 1.85 h, total body clearance (Cl(B)) 0.26 +/- 0.03 and 0.25 +/- 0.01 L/kg/h, volume of distribution at steady-state (V(d(ss))) 1.86 +/- 0.11 and 1.71 +/- 0.20 L/kg, area under curve (AUC) 76.31 +/- 9.17 and 119.21 +/- 2.05 microg.h/mL after i.v. injections of 20 and 30 mg/kg b.w. respectively. Serum concentration-time data after i.m. administration were adequately described by a one-compartment open model. The pharmacokinetic parameters were distribution half-lives (T(1/2k(a) )) 0.27 +/- 0.03 and 0.25 +/- 0.09 h, elimination half-lives (T(1/2k(e) )) 10.34 +/- 1.11 and 9.57 +/- 2.84 h, maximum concentrations (C(max)) 4.13 +/- 0.29 and 7.04 +/- 1.61 microg/mL, area under curve (AUC) 67.95 +/- 9.61 and 101.95 +/- 8.92 microg.h/mL, bioavailability (F) 89.04% and 85.52% after i.m. injections of 20 and 30 mg/kg b.w. respectively.  相似文献   

9.
A study on the bioavailability and pharmacokinetics of florfenicol was conducted in six healthy dogs following a single intravenous (i.v.) or oral (p.o.) dose of 20 mg kg(-1) body weight (b.w.). Florfenicol concentrations in serum were determined by a high-performance liquid chromatography/mass spectrometry. Plasma concentration-time data after p.o. or i.v. administration were analyzed by a non-compartmental analysis. Following i.v. injection, the total body clearance was 1.03 (0.49) L kg(-1)h(-1) and the volume of distribution at steady-state was 1.45 (0.82) L kg(-1). Florfenicol was rapidly distributed and eliminated following i.v. injection with 1.11 (0.94)h of the elimination half-life. After oral administration, the calculated mean C(max) values (6.18 microg ml(-1)) were reached at 0.94 h in dogs. The elimination half-life of florfenicol was 1.24 (0.64) h and the absolute bioavailability (F) was achieved 95.43 (11.60)% after oral administration of florfenicol. Florfenicol amine, the major metabolite of florfenicol, was detected in all dogs after i.v. and p.o. administrations.  相似文献   

10.
Florfenicol is a broad-spectrum bacteriostatic antibiotic used in domestic animals. The aim of the study was to determine the effect of florfenicol on the total number of lymphocytes in the thymus, spleen and mesenteric lymph nodes and the percentage and the absolute number of T cell subsets (CD4+CD8+, CD4-CD8-, CD4+, CD8+) in the thymus and T (CD3+, CD4+, CD8+) and B (CD19+) lymphocytes in the peripheral lymphatic organs in non-immunized mice and humoral immune response in sheep red blood cells (SRBC)-immunized mice. Florfenicol was administered orally at a dose of 30 mg/kg six times at 24 h intervals to non-immunized mice and four or seven times at 24 h intervals to SRBC-immunized mice. SRBC was injected 2 hours prior to the first dose of the drug. Florfenicol increased the percentage of CD4CD8- thymocytes and the absolute number of CD4+ and CD8+ thymocytes on day 7. The increased percentage and absolute number of CD3+, CD4+ and CD8+ lymphocytes in mesenteric lymph nodes and decreased percentage of lymphocytes B were also observed 24 hours from the last administration of florfenicol. Florfenicol administered after SRBC immunization reduced the number of plaque forming cells (PFC) and the production of anti-SRBC antibodies on days 4 and 7 after priming.  相似文献   

11.
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   

12.
The single-dose disposition kinetics of florfenicol was determined in healthy, non-lactating Egyptian goats, after its intravenous (i.v.) and intramuscular (i.m.) administration at 20 mg kg-1 b.wt. Drug concentrations in serum and urine were determined using microbiological assay method and data was subjected to a kinetic analysis. Florfenicol concentrations in serum decreased in a bi-exponential manner after intravenous administration with distribution (t1/2 alpha) and elimination (t1/2 beta) half-lives of 10.256 +/- 0.938 and 56.237 +/- 3.102 minute, respectively. The steady-state volume of distribution (Vdss) and total body clearance (Cltot) were 3.413 +/- 0.304 l kg-1 and 3.306 +/- 0.333 l kg h-1. After intramuscular administration, the peak serum concentration (Cmax) was 0.859 +/- 0.025 micrograms ml-1, achieved at (Tmax) 1.220 + 0.045 h. Florfenicol was detected in urine up to 24 and 96 hour after i.v. and i.m. administration, respectively. The extent of the protein binding and systemic bioavailability of florfenicol were 22.45 +/- 1.727% and 65.718 +/- 3.372%, respectively.  相似文献   

13.
OBJECTIVE: To determine the pharmacokinetics of ceftiofur sodium after IM and SC administration in green iguanas. ANIMALS: 6 male and 4 female adult green iguanas. PROCEDURE: In a crossover design, 5 iguanas received a single dose of ceftiofur sodium (5 mg/kg) IM, and 5 iguanas received the same dose SC. Blood samples were taken at 0, 20, and 40 minutes and 1, 2, 4, 8, 24, 48, and 72 hours after administration. After a 10-week washout period, each iguana was given the same dose via the reciprocal administration route, and blood was collected in the same fashion. Ceftiofur free-acid equivalents were measured via high-performance liquid chromatography. RESULTS: The first phase intercepts were significantly different between the 2 administration routes. Mean maximum plasma concentration was significantly higher with the IM (28.6 +/- 8.0 microg/mL) than the SC (18.6 +/- 8.3 microg/mL) administration route. There were no significant differences between terminal half-lives (harmonic mean via IM route, 15.7 +/- 4.7 hours; harmonic mean via SC route, 19.7 +/- 6.7 hours) and mean areas under the curve measured to the last time point (IM route, 11,722 +/- 7,907 microg x h/mL; SC route, 12,143 +/- 9,633 microg x h/mL). Ceftiofur free-acid equivalent concentrations were maintained > or = 2 microg/mL for > 24 hours via both routes. CONCLUSIONS AND CLINICAL RELEVANCE: A suggested dosing schedule for ceftiofur sodium in green iguanas for microbes susceptible at > 2 microg/mL would be 5 mg/kg, IM or SC, every 24 hours.  相似文献   

14.
OBJECTIVE: To determine concentrations of marbofloxacin in alveolar macrophages (AMs) and epithelial lining fluid (ELF) and compare those concentrations with plasma concentrations in healthy dogs. ANIMALS: 12 adult mixed-breed and purebred hounds. PROCEDURE: 10 dogs received orally administered marbofloxacin at a dosage of 2.75 mg/kg every 24 hours for 5 days. Two dogs served as nontreated controls. Fiberoptic bronchoscopy and bronchoalveolar lavage procedures were performed while dogs were anesthetized with propofol, approximately 6 hours after the fifth dose. The concentrations of marbofloxacin in plasma and bronchoalveolar fluid (cell and supernatant fractions) were determined by use of high-performance liquid chromatography with detection of fluorescence. RESULTS: Mean +/- SD plasma marbofloxacin concentrations 2 and 6 hours after the fifth dose were 2.36 +/- 0.52 microg/mL and 1.81 +/- 0.21 microg/mL, respectively. Mean +/- SD marbofloxacin concentration 6 hours after the fifth dose in AMs (37.43 +/- 24.61 microg/mL) was significantly greater than that in plasma (1.81 +/- 0.21 microg/mL) and ELF (0.82 +/- 0.34 microg/mL), resulting in a mean AM concentration-to-plasma concentration ratio of 20.4, a mean AM:ELF ratio of 60.8, and a mean ELF-to-plasma ratio of 0.46. Marbofloxacin was not detected in any samples from control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Marbofloxacin concentrations in AMs were greater than the mean inhibitory concentrations of major bacterial pathogens in dogs. Results indicated that marbofloxacin accumulates in AMs at concentrations exceeding those reached in plasma and ELF The accumulation of marbofloxacin in AMs may facilitate treatment for susceptible intracellular pathogens or infections associated with pulmonary macrophage infiltration.  相似文献   

15.
Blood pressure during anesthesia and surgery was compared for 2 groups of horses. Group A, consisting of 23 horses, had a tourniquet placed on the distal portion of a limb. The other group of 20 horses (group B) had surgery of comparable nature and duration as did group-A horses, but a tourniquet was not used. There was a statistical difference (P less than 0.05) in the peak systolic arterial blood pressure between the groups; group-A horses had a mean (+/- SEM) peak of 151 +/- 6 mm of Hg and group-B horses had a peak of 118 +/- 4 mm of Hg. In addition, group-A horses had immediate decrease in blood pressure, coincident with tourniquet deflation. The blood pressure decrease of 23 +/- 3 mm of Hg represented 16% of immediate predeflation blood pressure. Comparable blood pressure decrease was not observed at the end of surgery in group-B horses. Significant difference was not found when other factors that could affect blood pressure were considered. These factors included preanesthetic medication, anesthetic agents, mode of ventilation, pretourniquet inflation blood pressure, and duration of tourniquet inflation. Significant (P less than 0.05) difference in peak blood pressure was observed when the tourniquet was placed on the dependent, compared with the uppermost, limb, with changes more pronounced when the tourniquet was placed on the dependent limb. Tourniquet placement was associated with hypertension, and tourniquet deflation was associated with blood pressure decrease in these anesthetized horses.  相似文献   

16.
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   

17.
This study evaluated the pharmacokinetics of florfenicol in the white-spotted bamboo shark (Chiloscyllium plagiosum). In addition to the pharmacokinetics, the potential application for treatment of bacterial meningitis was explored. A pilot study was used to compare doses of 30, 40, and 50 mg/kg i.m. Following that study, 10 adult sharks were administered a single i.m. dose of florfenicol at 40 mg/kg. Plasma and cerebrospinal fluid were collected and analyzed for florfenicol by a sensitive and specific high-pressure liquid chromatographic method. Pharmacokinetic analysis was performed using both non-compartmental and compartmental techniques. The absorption produced an average peak at 54 (+/-19) hr from the i.m. site of administration, and the half-life was prolonged, averaging 269.79 hr (+/-135.87). Florfenicol plasma concentrations peaked at an average of 11.85 microg/ml (+/-1.45) and were maintained above our target minimum inhibitory concentration of 4-8 microg/ml for at least 120 hr. Cerebrospinal fluid concentrations peaked at an estimated 9 microg/ml around 48 hr, surpassing the target minimum inhibitory concentration for at least 72 hr.  相似文献   

18.
OBJECTIVE: To determine radiocarpal (RC) joint synovial fluid and plasma ceftiofur concentrations after regional intravenous perfusion (RIP) and systemic intravenous (IV) administration. STUDY DESIGN: Experimental cross-over study. ANIMALS: Five normal adult horses. METHODS: One RC joint was randomly selected for RIP and the contralateral RC joint was sampled to determine intrasynovial ceftiofur concentrations after IV administration. Wash-out between IV and RIP was > or = 14 days. After surgical introduction of an intraarticular catheter, ceftiofur (2 g) was administered under general anesthesia either IV or by RIP after tourniquet application. Plasma and synovial fluid were collected over 24 hours. Samples were analyzed using high-performance liquid chromatography with ultraviolet detection and the results were statistically analyzed using a linear mixed effect model. RESULTS: Mean synovial fluid ceftiofur concentrations were consistently higher after RIP than after IV administration and were > 1 mug/mL (minimal inhibitory concentration [MIC] for common pathogens) for >24 hours. Mean synovial fluid peak concentration of ceftiofur after RIP and IV administration was 392.7+/-103.29 microg/mL at 0.5 hours postinjection (HPI) and 2.72+/-0.31 mug/mL at 1 HPI, respectively. Large variations in synovial fluid and plasma ceftiofur concentrations were observed between horses regardless of administration technique. RIP did not cause adverse effects. CONCLUSIONS: Under the present experimental conditions RIP with ceftiofur (2 g) induced significantly higher intraarticular antibiotic concentrations in the RC joint in comparison with IV administration. Moreover, after RIP, synovial fluid ceftiofur concentrations remain above the MIC for common pathogens (1 microg/mL) for > 24 hours. No adverse effects from the technique or the antibiotic were observed. CLINICAL RELEVANCE: RIP with high doses of ceftiofur may be a beneficial adjunctive therapy when treating equine synovial infections which are caused by cephalosporin susceptible microorganisms.  相似文献   

19.
OBJECTIVE: To develop a high-performance liquid chromatography (HPLC) assay for cetirizine in feline plasma and determine the pharmacokinetics of cetirizine in healthy cats after oral administration of a single dose (5 mg) of cetirizine dihydrochloride. ANIMALS: 9 healthy cats. PROCEDURES: Heparinized blood samples were collected prior to and 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after oral administration of 5 mg of cetirizine dihydrochloride to each cat (dosage range, 0.6 to 1.4 mg/kg). Plasma was harvested and analyzed by reverse-phase HPLC. Plasma concentrations of cetirizine were analyzed with a compartmental pharmacokinetic model. Protein binding was measured by ultrafiltration with a microcentrifugation system. RESULTS: No adverse effects were detected after drug administration in the cats. Mean +/- SD terminal half-life was 10.06 +/- 4.05 hours, and mean peak plasma concentration was 3.30 +/- 1.55 microg/mL. Mean volume of distribution and clearance (per fraction absorbed) were 0.24 +/- 0.09 L/kg and 0.30 +/- 0.09 mL/kg/min, respectively. Mean plasma concentrations were approximately 2.0 microg/mL or higher for 10 hours and were maintained at > 0.72 microg/mL for 24 hours. Protein binding was approximately 88%. CONCLUSIONS AND CLINICAL RELEVANCE: A single dose of cetirizine dihydrochloride (approx 1 mg/kg, which corresponded to approximately 0.87 mg of cetirizine base/kg) was administered orally to cats. It was tolerated well and maintained plasma concentrations higher than those considered effective in humans for 24 hours after dosing. The half-life of cetirizine in cats is compatible with once-daily dosing, and the extent of protein binding is high.  相似文献   

20.
OBJECTIVE: To evaluate the pharmacokinetic-pharmacodynamic parameters of enrofloxacin and a low dose of amikacin administered via regional IV limb perfusion (RILP) in standing horses. ANIMALS: 14 adult horses. PROCEDURES: Standing horses (7 horses/group) received either enrofloxacin (1.5 mg/kg) or amikacin (250 mg) via RILP (involving tourniquet application) in 1 forelimb. Samples of interstitial fluid (collected via implanted capillary ultrafiltration devices) from the bone marrow (BMIF) of the third metacarpal bone and overlying subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joint were collected prior to (time 0) and at intervals after tourniquet release for determination of drug concentrations. For pharmacokinetic-pharmacodynamic analyses, minimum inhibitory concentrations (MICs) of 16 microg/mL (amikacin) and 0.5 microg/mL (enrofloxacin) were applied. RESULTS: After RILP with enrofloxacin, 3 horses developed vasculitis. The highest synovial fluid concentrations of enrofloxacin and amikacin were detected at time 0; median values (range) were 13.22 microg/mL (0.254 to 167.9 microg/mL) and 26.2 microg/mL (5.78 to 50.0 microg/mL), respectively. Enrofloxacin concentrations exceeded MIC for approximately 24 hours in STIF and synovial fluid and for 36 hours in BMIF. After perfusion of amikacin, concentrations greater than the MIC were not detected in any samples. Effective therapeutic concentrations of enrofloxacin were attained in all samples. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with orthopedic infections, RILP of enrofloxacin (1.5 mg/kg) should be considered as a treatment option. However, care must be taken during administration. A dose of amikacin > 250 mg is recommended to attain effective tissue concentrations via RILP in standing horses.  相似文献   

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