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1.
OBJECTIVE: To assess gentamicin concentrations in serum and bronchial lavage fluid (BLF) of horses during a 24-hour period after once-daily aerosol administration of gentamicin (GAER) for 7 days and the pattern and degree of bronchial tree inflammation associated with repeated GAER. ANIMALS: 13 healthy adult horses (9 geldings and 4 mares). PROCEDURE: The treatment group comprised 8 horses, and 5 horses were untreated control animals. Gentamicin (20 mL of gentamicin [50 mg/mL]) was administered via aerosol once daily for 7 days. Samples of serum and BLF were obtained from all horses before GAER and 0.5, 4, 8, and 24 hours after the final day of GAER. Gentamicin concentrations were determined for all samples from treated horses, and cytologic examinations were performed on all BLF samples. RESULTS: Peak median BLF gentamicin concentration detected at 0.5 hours was 2.50 microg/mL. Median serum gentamicin concentration was < 0.50 microg/mL at all time points. Significant differences were not observed in total nucleated cell counts or differential cell counts in BLF between groups at any time point. Neutrophil count in BLF for all horses was increased over baseline at 4 and 24 hours. CONCLUSIONS AND CLINICAL RELEVANCE: We did not detect evidence of gentamicin accumulation or respiratory inflammation after once-daily GAER for 7 days. This protocol appears unlikely to result in local or systemic toxicosis. Repeated daily GAER to horses appears to be a safe procedure and may have clinical use in the treatment of horses with bacterial infections of the airways.  相似文献   

2.
The concentration of gentamicin in plasma and synovial fluid of normal adult horses was measured periodically for 24 hours after IV (2.2 mg/kg of body weight), intra-articular (IA; 150 mg), and simultaneous IV and IA administrations. Gentamicin also was buffered with sodium bicarbonate (3 mEq) and then was administered IA and simultaneously IV and IA. Synovial fluid specimens were obtained via an indwelling catheter placed into the antebrachiocarpal joint. The peak mean plasma gentamicin concentration (8.30 micrograms/ml) after IV administration was significantly (P less than 0.05) greater than that (0.69 microgram/ml) after IA administration of gentamicin and that (0.55 microgram/ml) after administration of gentamicin buffered with sodium bicarbonate. Gentamicin concentration greater than a therapeutic concentration was not attained in the plasma after IA administration of buffered or unbuffered gentamicin. The peak mean synovial fluid concentration (1,828 micrograms/ml) after IA administration of unbuffered gentamicin was significantly (P less than 0.05) greater than that (2.53 micrograms/ml) after IV administration and significantly (P less than 0.05) less than that (5,720 micrograms/ml) after simultaneous IV and IA administration. The peak mean synovial fluid concentration after IA administration of buffered gentamicin, with and without simultaneous IV administration (2,128 and 2,680 micrograms/ml, respectively), was not significantly different than that after IA treatment with unbuffered gentamicin. Mean synovial fluid concentration did not differ significantly between groups after IA administration of gentamicin in any combination at postinjection hours 8, 12, and 24, but remained significantly (P less than 0.05) greater than that at the same times after IV administration.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

3.
OBJECTIVE: To compare gentamicin concentrations achieved in synovial fluid and joint tissues during IV administration and continuous intra-articular (IA) infusion of the tarsocrural joint in horses. ANIMALS: 18 horses with clinically normal tarsocrural joints. PROCEDURE: Horses were assigned to 3 groups (6 horses/group) and administered gentamicin (6.6 mg/kg, IV, q 24 h for 4 days; group 1), a continuous IA infusion of gentamicin into the tarsocrural joint (50 mg/h for 73 hours; group 2), or both treatments (group 3). Serum, synovial fluid, and joint tissue samples were collected for measurement of gentamicin at various time points during and 73 hours after initiation of treatment. Gentamicin concentrations were compared by use of a Kruskal-Wallis ANOVA. RESULTS: At 73 hours, mean +/- SE gentamicin concentrations in synovial fluid, synovial membrane, joint capsule, subchondral bone, and collateral ligament of group 1 horses were 11.5 +/- 1.5 microg/mL, 21.1 +/- 3.0 microg/g, 17.1 +/- 1.4 microg/g, 9.8 +/- 2.0 microg/g, and 5.9 +/- 0.7 microg/g, respectively. Corresponding concentrations in group 2 horses were 458.7 +/- 130.3 microg/mL, 496.8 +/- 126.5 microg/g, 128.5 +/- 74.2 microg/g, 99.4 +/- 47.3 microg/g, and 13.5 +/- 7.6 microg/g, respectively. Gentamicin concentrations in synovial fluid, synovial membrane, and joint capsule of group 1 horses were significantly lower than concentrations in those samples for horses in groups 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE: Continuous IA infusion of gentamicin achieves higher drug concentrations in joint tissues of normal tarsocrural joints of horses, compared with concentrations after IV administration.  相似文献   

4.
OBJECTIVE: To evaluate pharmacokinetics of once daily i.v. administration of gentamicin sulfate to adult horses that had abdominal surgery. DESIGN: Prospective study. ANIMALS: 28 adult horses that underwent abdominal surgery for colic. PROCEDURE: 14 horses were treated with each dosage of gentamicin (i.e., 6.6 or 4 mg/kg, i.v., q 24 h) and blood samples were collected for pharmacokinetic analysis. Plasma gentamicin concentrations were measured by use of a fluorescence polarization immunoassay. Pharmacokinetic analysis measured the elimination half-life, volume of distribution, and gentamicin total systemic clearance. Treatment outcome, CBC, and serum creatinine concentrations were recorded. RESULTS: 1 horse in the high-dosage group died. All other horses successfully recovered, and did not develop bacterial infection or have evidence of drug toxicosis resulting in renal injury. Mean pharmacokinetic variables for gentamicin administration at a high or low dosage (i.e., 6.6 or 4 mg/kg, i.v., q 24 h) were half-life of 1.47 and 1.61 hours, volume of distribution of 0.17 and 0.17 L/kg, and systemic clearance of 1.27 and 1.2 ml/kg/min, respectively. Mean serum creatinine concentration was 1.74 and 1.71 for the high and low dosages, respectively, and serum creatinine concentration was not correlated with gentamicin clearance. CONCLUSIONS AND CLINICAL RELEVANCE: Gentamicin administration at a dosage of 4 mg/kg, i.v., every 24 hours, will result in plasma concentrations that are adequate against susceptible bacteria with a minimum inhibitory concentration (MIC) of < or = 2.0 micrograms/ml. Gentamicin administration at a calculated dosage of 6.8 mg/kg, i.v., every 24 hours will result in optimum plasma concentrations against susceptible bacteria with a MIC of < or = 4.0 micrograms/ml.  相似文献   

5.
Objective— To compare intra-articular (IA) and bone gentamicin concentrations achieved after intra-articular administration or regional intravenous perfusion (RIP).
Study Design— Experimental study.
Animals— Twelve healthy adult horses.
Methods— Horses were assigned to 2 treatment groups (  n = 6/group  ): Group 1, 1 g gentamicin administered simultaneously in both left and right metacarpophalangeal joints and group 2, 1 g gentamicin administered simultaneously in both left and right lateral palmar veins. Serum, synovial fluid, and bone biopsy specimens were collected. Gentamicin concentrations were determined by fluorescence polarization immunoassay. Bone, synovial fluid, and serum gentamicin concentrations were compared over time and between groups using 2-way ANOVA. Significance of all tests were evaluated at   P < .05  .
Results— IA metacarpophalangeal joint administration resulted in higher concentration of gentamicin in synovial fluid than RIP administration. Synovial fluid concentration remained above minimum inhibitory concentration (MIC) for common pathogens for over 24 hours with IA and RIP administration. Bone gentamicin concentration remained above MIC for 8 hours with both methods; there was no significant difference in gentamicin concentration in bone with either method. Neither IA nor RIP administration had a significant effect on serum concentration of gentamicin.
Conclusions— In normal horses, there is no difference in bone gentamicin concentration obtained with IA or RIP administration.
Clinical Relevance— Based on MIC for common equine pathogens, administration of gentamicin intra-articularly or by regional intravenous perfusion should be useful for treatment of osteomyelitis.  相似文献   

6.
The effect of gentamicin sulfate, unbuffered and buffered with sodium bicarbonate, on synovial fluid and membrane of clinically normal equine joints was evaluated. Thirty-six adult horses with clinically normal antebrachiocarpal joints were allotted to 6 treatment groups of 6 horses each. One antebrachiocarpal joint in each horse was chosen for treatment. Group-1 horses were given gentamicin (3 ml; 50 mg/ml); group-2 horses were given sodium bicarbonate (3 ml; 1 mEq/ml); group-3 horses were given gentamicin (3 ml; 50 mg/ml) and sodium bicarbonate (3 ml; 1 mEq/ml); group-4 horses were not treated; and horses of groups 5 and 6 were given polyionic physiologic solution (3 and 6 ml, respectively). Synovial fluid specimens were obtained from 5 horses of each group for cytologic analysis at postinjection hours (PIH) 0, 24, 72, and 192 and for pH determination at PIH 0, 0.25, 0.5, 1, 4, 8, 24, 72, and 192. The sixth horse of each group was euthanatized at PIH 24, and the synovial membrane of the treated and contralateral (nontreated) antebrachiocarpal joints was examined macroscopically and microscopically. After intra-articular gentamicin administration, the mean synovial fluid pH was lowest (5.98) at PIH 0.25, but by PIH 8, it was not significantly different from the control value (group-5 horses). When sodium bicarbonate was combined with gentamicin before intra-articular administration, the mean synovial fluid pH was lowest (7.07) at PIH 0.25, but by PIH 1, it was not significantly different from the control value (group-6 horses).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

7.
OBJECTIVE: To develop a method for continuous infusion of gentamicin into the tarsocrural joint of horses, to determine pharmacokinetics of gentamicin in synovial fluid of the tarsocrural joint during continuous infusion, and to evaluate effects of continuous infusion of gentamicin on characteristics of the synovial fluid. ANIMALS: 12 healthy adult horses. PROCEDURE: An infusion catheter consisting of flow control tubing connected to a balloon infuser was used. Gentamicin solution (100 mg/ml) was infused in the right tarsocrural joint and balanced electrolyte solution was infused in the left tarsocrural joint for 5 days. Synovial fluid and serum gentamicin concentrations were measured by use of a fluorescence polarization immunoassay. RESULTS: 17 of the 24 (71%) infusion catheters initially placed functioned without complications for the entire 5-day infusion period. Median gentamicin concentration in synovial fluid from treated joints during the 5-day infusion period ranged from 2875 to 982 microg/ml. Median serum gentamicin concentration during this period ranged from 2.31 to 2.59 microg/ml. Mean (+/- SD) elimination half-life and total clearance of gentamicin from the synovial fluid were 6.25+/-1.01 hours and 1.52+/-0.96 ml/min, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: An infusion catheter can be used for continuous infusion of gentamicin into the tarsocrural joints of horses for up to 5 days. At a gentamicin dosage of 0.17+/-0.02 mg/kg/h, continuous intra-articular infusion results in synovial fluid gentamicin concentrations greater than 100 times the minimal inhibitory concentration reported for common equine pathogens.  相似文献   

8.
Septic arthritis was induced in one antebrachiocarpal joint of seven horses by the intra-articular injection of 1 mL Staphylococcus aureus suspension containing a mean of 10(5) colony-forming units. Twenty-four hours after inoculation, four horses were treated by regional perfusion with 1 g of gentamicin sulfate, and three horses received 2.2 mg/kg gentamicin sulfate intravenously (IV) every 6 hours. Synovial fluid was collected for culture and cytology at regular intervals, and the synovial membranes were collected for culture and histologic examination at euthanasia 24 hours after the first treatment. Gentamicin concentration in the septic synovial fluid after three successful perfusions was 221.2 +/- 71.4 (SD) micrograms/mL; after gentamicin IV, it was 7.6 +/- 1.6 (SD) micrograms/mL. The mean leukocyte count in the inoculated joints decreased significantly by hour 24 in the successfully perfused joints. Terminal bacterial cultures of synovial fluid and synovial membranes were negative in two horses with successfully perfused joints. S. aureus was isolated from the infected joints in all three horses treated with gentamicin IV.  相似文献   

9.
Chemical and cytologic effects and bactericidal activity of gentamicin in septic synovial fluid were evaluated in an experimental model of infectious arthritis in horses. Septic arthritis was induced by inoculation of approximately 7.5 X 10(6) colony-forming units of Escherichia coli into 1 antebrachiocarpal joint in each of 16 clinically normal adult horses. Clinical signs of septic arthritis were evident 24 hours after inoculation. Horses were allotted to 3 groups: group-1 horses (n = 5) each were given 150 mg of gentamicin (50 mg/ml; 3 ml) intra-articularly (IA); group-2 horses (n = 5) each were given 2.2 mg of gentamicin/kg of body weight, IV, every 6 hours; and group-3 horses (n = 6) each were given buffered gentamicin, consisting of 3 mEq of sodium bicarbonate (1 mEq/ml; 3 ml) and 150 mg of gentamicin (50 mg/ml; 3 ml), IA. Synovial fluid specimens were obtained at posttreatment hour (PTH) 0, 0.25, 1, 4, 8, 12, and 24 via an indwelling intra-articular catheter. Synovial fluid pH was evaluated at PTH 0, 0.25, and 24. Microbiologic culture and cytologic examination were performed on synovial fluid specimens obtained at PTH 0 and 24, and gentamicin concentration was measured in all synovial fluid specimens. At PTH 0, E coli was isolated from synovial fluid specimens obtained from all horses. Synovial fluid pH was lower (range, 7.08 to 7.16) and WBC count was higher (range, 88,000 to 227,200 cells/microliters) and predominantly neutrophilic (95 to 99%) at PTH 0 than before inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

10.
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   

11.
Plasma concentration of gentamicin was measured 1, 4, and 6 hours after IV administration in 35 hospitalized adult horses on days 1, 3, 5, and 10 of treatment. The mean apparent elimination rate constant beta was 0.53 +/- 0.10 h-1 on day 1 for horses with normal plasma creatinine concentration and 0.41 +/- 0.13 h-1 for horses with abnormally high plasma creatinine concentration. There was no significant difference between beta of the hospitalized horses and of 6 healthy horses treated with gentamicin, but total clearance for the hospitalized horses with normal plasma creatinine concentration was significantly greater than that of the healthy horses and the hospitalized horses with abnormally high plasma creatinine concentration. Gentamicin clearance was significantly correlated with plasma creatinine concentration for healthy horses and hospitalized horses, and beta was significantly correlated with plasma creatinine concentration for hospitalized horses. Twelve of the 35 hospitalized horses required an adjustment in gentamicin dosage. Ten required a reduction, 1 an increase, and 1 a change in dosage and interval with no net change in total daily dose. One horse of 35 (2.9%) developed signs compatible with nephrotoxicosis on day 14 of treatment, despite appropriate gentamicin concentrations on day 10.  相似文献   

12.
Gentamicin sulfate-induced nephrotoxicosis was compared in 2 groups of horses fed different rations. Four horses were fed only alfalfa hay, and 4 other horses were fed only whole oats. Seven days after initiation of the diet, all horses were given gentamicin IV (5 mg/kg of body weight) every 12 hours for 22 days. Urinary gamma-glutamyl-transferase to urinary creatinine (UGGT:UCr) ratio was calculated daily, and serum concentration of gentamicin was measured at 1 and 12 hours after drug administration. Results indicated that horses fed oats had greater renal tubular damage than did horses fed alfalfa. Mean UGGT:UCr for horses fed alfalfa was 47.1 +/- 18.8 and was 100.0 +/- 19.0 for horses fed oats (P = 0.007). The UGGT:UCr in horses fed oats was greater than 100 for a total of 54 days; horses fed alfalfa had UGGT:UCr greater than 100 for only 7 days. Two horses not given gentamicin were fed only oats and 2 were fed only alfalfa. These horses had mean UGGT:UCr of 17.6 +/- 2.2 and 30.5 +/- 3.0, respectively. Mean peak and trough concentrations of gentamicin were statistically different for horses fed oats and those fed alfalfa (peak 23.16 +/- 1.87 and 14.07 +/- 1.79 micrograms/ml, respectively [P = 0.0001], and trough, 1.81 +/- 0.69 and 0.71 +/- 0.70 micrograms/ml, respectively [P = 0.0270]). Mean half-lives of gentamicin (estimated from peak and trough concentrations) for horses fed alfalfa (2.58 +/- 0.26 hours) and horses fed oats (2.88 +/- 0.27 hours) were not significantly different. Horses fed only oats had greater degree of gentamicin-induced nephrotoxicosis than did those fed only alfalfa.  相似文献   

13.
Healthy mature pony mares (n = 6) were given a single dose of gentamicin (5 mg/kg of body weight) IV or IM 8 days apart. Venous blood samples were collected at 0, 5, 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 30, 36, 40, and 48 hours after IV injection of gentamicin, and at 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, and 30 hours after IM injection of gentamicin. Gentamicin serum concentration was determined by a liquid-phase radioimmunoassay. The combined data of IV and IM treatments were analyzed by a nonlinear least-square regression analysis program. The kinetic data were best fitted by a 2-compartment open model, as indicated by residual trends and improvements in the correlation of determination. The distribution phase half-life was 0.12 +/- 0.02 hour and postdistribution phase half-life was 1.82 +/- 0.22 hour. The volume of the central compartment was 115.8 +/- 6.0 ml/kg, volume of distribution at steady state was 188 +/- 9.9 ml/kg, and the total body clearance was 1.27 +/- 0.18 ml/min/kg. Intramuscular absorption was rapid with a half-life for absorption of 0.64 +/- 0.14 hour. The extent of absorption was 0.87 +/- 0.14. Kinetic calculations predicted that IM injections of 5 mg of gentamicin/kg every 8 hours would provide average steady-state serum concentrations of 7.0 micrograms/ml, with maximum and minimum steady-state concentrations of 16.8 and 1.1 micrograms/ml, respectively.  相似文献   

14.
The purpose of this study was to determine the pharmacokinetic values for gentamicin in neonatal calves and to compare these values with those in adult cattle (cows). Gentamicin (4 mg/kg of body weight) was administered IV to 7 Holstein bull calves on days 1 (between 12 and 24 hours of age), 5, 10, and 15 after birth, and was administered once IV to 7 Holstein cows. Serum was collected from each animal before administration and at 22 different time intervals from 2 to 400 minutes after injection. Sera were analyzed for gentamicin concentrations. Decay of serum gentamicin concentrations was best described by a 2-compartment pharmacokinetic model. Elimination half-life (t1/2 (beta)) of gentamicin decreased from day 1 (149 minutes) to day 5 (119 minutes), but did not change between days 5 and 15 (111 minutes). Compared with the t1/2(beta) in 1- and 15-day-old calves, the t 1/2 (beta) in cows was shorter (76 minutes). In the calves, apparent volume of distribution (based on total area under the disposition curve) did not change between 1 (393 ml/kg) and 5 (413 ml/kg) days of age, decreased on day 10 (341 ml/kg) and cows day 15 (334 ml/kg), and was markedly smaller than that in cows (140 ml/kg). Total body clearance of gentamicin in cows (1.29 ml/min X kg) was lower than that seen in calves on day 1 (1.92 ml/min X kg) and on day 15 (2.10 ml/min X kg). The decrease in apparent volume of distribution of gentamicin was mirrored by a large decrease in the extracellular fluid volume, as measured by inulin space.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

15.
The administration of antibiotics by aerosol to horses suffering from respiratory infections may partially circumvent the limitations of antimicrobial therapy, e.g. large injection volumes, low bioavailability and risk of diarrhoea. Only injectable formulations are available currently and usually contain other substances that could irritate the mucosa and induce coughing and bronchospasm. In addition, the quality of the aerosol, particularly in terms of the delivery of antibiotics to the deep parts of the lung, is unknown. Although used under field conditions, cefquinome delivered by aerosol has never been studied in horses. This study examined the safety of cefquinome injectable solution, administered by aerosol at a dose of 225 mg/inhalation to 7 healthy horses, by assessing (1) pulmonary function before and 15 min after a single inhalation, at the first day (Day 1) and the fifth day (Day 5) of a 5 day period treatment; and (2) the inflammatory status of the lung, i.e. percentage neutrophils and myeloperoxidase concentration, based on bronchoalveolar lavage (BAL) at D1 and D5. In addition, cefquinome concentrations were measured in bronchoalveolar lavage fluid after aerosol, intravenous (i.v.) and intramuscular (i.m.) administrations. A single aerosol of cefquinome injectable solution did not induce any immediate nor delayed pulmonary side effects in healthy horses and produced cefquinome concentrations in bronchoalveolar lavage (BAL) within 30 min that were higher than the minimal inhibitory concentration of the main equine respiratory pathogens. These results should stimulate further studies, especially in horses suffering from bronchial hyper‐reactivity. Aerosol delivery of antibiotics may well have a role in equine therapeutics.  相似文献   

16.
Gentamicin sulfate (2.2 mg/kg of body weight, IV) was given to anesthetized horses. Jejunal and large colon tissue samples (1 g), serum, and urine were collected over a 4-hour period. Maximum gentamicin concentrations in serum (10.06 +/- 2.85 micrograms/ml) occurred at 0.25 hours after injection. Maximum gentamicin concentrations in the large colon (4.13 +/- 1.80 micrograms/ml) and jejunum (2.26 +/- 1.35 micrograms/ml) occurred in horses at 0.5 and 0.33 hours, respectively. Tissue concentrations decreased in parallel with serum concentrations and were still detectable at the end of the 4-hour period. During the time that samples were collected, the total amount of gentamicin excreted in the urine ranged from 7.21 +/- 3.11 mg to 11.91 +/- 7.12 mg, with a mean urinary concentration of 57.01 +/- 5.37 micrograms/ml. Over the 4-hour collection period, the fraction of dose that was excreted unchanged in the urine was 4.8 +/- 1.9%. Pharmacokinetic analyses of the serum concentration-time data gave a serum half-life of 2.52 +/- 1.29 hours, volume of distribution of 227 +/- 83 ml/kg, and body clearance of 1.12 +/- 0.26 ml/min/kg. The half-lives of the antibiotic in the jejunum and large colon were 1.32 and 1.33 hours, respectively.  相似文献   

17.
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   

18.
OBJECTIVE: To determine the pharmacokinetics of fluconazole in horses. ANIMALS: 6 clinically normal adult horses. PROCEDURE: Fluconazole (10 mg/kg of body weight) was administered intravenously or orally with 2 weeks between treatments. Plasma fluconazole concentrations were determined prior to and 10, 20, 30, 40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after administration. A long-term oral dosing regimen was designed in which all horses received a loading dose of fluconazole (14 mg/kg) followed by 5 mg/kg every 24 hours for 10 days. Fluconazole concentrations were determined in aqueous humor, plasma, CSF, synovial fluid, and urine after administration of the final dose. RESULTS: Mean (+/- SD) apparent volume of distribution of fluconazole at steady state was 1.21+/-0.01 L/kg. Systemic availability and time to maximum plasma concentration following oral administration were 101.24+/-27.50% and 1.97+/-1.68 hours, respectively. Maximum plasma concentrations and terminal half-lives after IV and oral administration were similar. Plasma, CSF, synovial fluid, aqueous humor, and urine concentrations of fluconazole after long-term oral administration of fluconazole were 30.50+/-23.88, 14.99+/-1.86, 14.19+/-5.07, 11.39+/-2.83, and 56.99+/-32.87 microg/ml, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Bioavailability of fluconazole was high after oral administration to horses. Long-term oral administration maintained plasma and body fluid concentrations of fluconazole above the mean inhibitory concentration (8.0 mg/ml) reported for fungal pathogens in horses. Fluconazole may be an appropriate agent for treatment of fungal infections in horses.  相似文献   

19.
Single and multiple dose gentamicin regimens were compared in sheep to determine the relevant pharmacokinetic differences. Seven mature sheep were given 10 mg/kg of gentamicin by IV bolus. Serum concentrations were monitored for 19 days. Four weeks after the initial bolus, gentamicin was administered IM (3 mg/kg every 8 hours) for 7 days. Ewes were euthanatized and necropsied at 1, 8, and 15 days after termination of the IM regimen and the tissues were assayed for gentamicin. Serum concentrations were analyzed using a triexponential equation. The IV kinetic studies revealed an alpha half-life (t1/2) of 0.31 +/- 0.14 hours, beta t1/2 of 2.4 +/- 0.5 hours, and gamma t1/2 of 30.4 +/- 18.9 hours. Multiple IM dose kinetic studies revealed a beta t1/2 of 2.8 +/- 0.6 hours and gamma t1/2 of 82.1 +/- 17.8 hours. After multiple dosing, gamma t1/2 was significantly longer than after the single IV bolus (P less than 0.05). Twenty-four hour urine collection accounted for 75% to 80% of the total IV dose. Renal cortical gentamicin concentration reached 224 micrograms/g of tissue and then decreased, with a 90-hour t1/2. Renal medullary gentamicin concentration reached 18 micrograms/g with a 42-day t1/2. After multiple dosing, liver gentamicin concentration reached 11 micrograms/g and skeletal muscle concentrations were less than or equal to 0.6 micrograms/g. Route or duration of administration significantly affected the gamma-phase serum concentrations, which may influence gentamicin nephrotoxicosis. The present study also illustrated the complexities in predicting aminoglycoside withdrawal times for food-producing animals before slaughter.  相似文献   

20.
OBJECTIVE: To determine whether iontophoretic administration of dexamethasone to horses results in detectable concentrations in synovial fluid, plasma, and urine. ANIMALS: 6 adult mares. PROCEDURE: Iontophoresis was used to administer dexamethasone. Treatments (4 mA for 20 minutes) were administered to a tarsocrural joint of each mare. The drug electrode contained 3 ml of dexamethasone sodium phosphate at a concentration of 4 or 10 mg/ml. Samples of synovial fluid, blood, and urine were obtained before and 0.5, 4, 8, and 24 hours after each treatment. All samples were tested for dexamethasone using an ELISA. Synovial fluid also was evaluated for dexamethasone, using high-performance liquid chromatography. RESULTS: The lower and upper limits of detection for dexamethasone in synovial fluid with the ELISA were 0.21 and 1.5 ng/ml, respectively. Dexamethasone administered at a concentration of 10 mg/ml was detected by the ELISA in synovial fluid of 5 mares from 0.5 to 24 hours and in urine of 4 mares from 0.5 to 8 hours after each treatment, but it was not detected in plasma. Mean synovial fluid concentration of dexamethasone was 1.01 ng/ml. Dexamethasone administered at a concentration of 4 mg/ml was detected by the ELISA in urine of 2 mares at 0.5 and 4 hours after treatment, but it was not detected in synovial fluid or plasma. CONCLUSIONS AND CLINICAL RELEVANCE: Iontophoresis cannot be considered an effective method for delivery of dexamethasone to synovial fluid of horses, because drug concentrations achieved in this study were less than therapeutic concentrations.  相似文献   

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