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1.
OBJECTIVE: To determine the pharmacokinetics of potassium bromide (KBr) in horses after single and multiple oral doses. ANIMALS: Twelve adult Standardbred and Thoroughbred mares. PROCEDURE: Horses were randomly assigned to two treatment groups. Group 1 horses were given a single oral dose of 120 mg/kg potassium bromide. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of KBr were measured to construct concentration versus time curves and to calculate pharmacokinetic parameters. Treated horses were monitored twice daily by clinical examination. Serum concentrations of sodium, potassium and chloride ions and partial pressures of venous blood gases were determined. RESULTS: Maximum mean serum concentration following a single dose of KBr (120 mg/kg) was 423 +/- 22 microg/mL and the mean elimination half-life was 75 +/- 14 h. Repeated administration of a loading dose of KBr (120 mg/kg once daily for 5 d) gave a maximum serum concentration 1639 +/- 156 microg/mL. The administration of lower, maintenance doses (40 mg/kg once daily) was associated with decreased serum bromide concentrations, which plateaued at approximately 1000 microg/mL. Administration of KBr was associated with significant but transient changes in serum potassium and sodium concentrations, and possible changes in base excess and plasma bicarbonate concentrations. High serum concentrations of bromide were associated with an apparent increase in serum chloride concentrations, when measured on an ion specific electrode. CONCLUSIONS: and clinical relevance Loading doses of 120 mg/kg daily over 5 d and maintenance doses of approximately 90 mg/kg of KBr administered once daily resulted in serum bromide concentrations consistent with therapeutic efficacy for the management of seizures in other species. The clinical efficacy of this agent as an anticonvulsant medication and/or calmative in horses warrants further investigation.  相似文献   

2.
The purpose of this study was to describe the pharmacokinetics of bromide in horses and to evaluate the corrected bromide space as an indicator of extracellular fluid volume (ECFV) in horses after the administration of a single dose of bromide by intravenous infusion. Sodium bromide (30 mg/kg of body weight, IV) was administered to 6 clinically healthy mares over a period of 3 minutes. Blood samples were collected before infusion and at intervals between 0.5 hours and 53 days after infusion. Mean elimination half-life (harmonic mean) was 126 hours (5.2 days), clearance was 1.4 +/- 0.09 mL/(kg x h), area under the curve was 17,520 +/- 1,100 microg x h/mL. and volume of distribution (steady state) was 0.255 +/- 0.015 L/kg. The mean corrected bromide space was determined from the volume of distribution (steady state) and the serum concentrations of bromide at equilibration. Corrected bromide space, an estimate of ECFV, was 0.218 +/- 0.01 L/kg. The conclusion was made that ECFV of horses can be estimated by measuring bromide concentrations in a preinfusion serum sample and a sample obtained 5 hours after the administration of bromide.  相似文献   

3.
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   

4.
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   

5.
OBJECTIVE: To determine pharmacokinetic parameters for meloxicam, a nonsteroidal anti-inflammatory drug, in horses. ANIMALS: 8 healthy horses. PROCEDURE: In the first phase of the study, horses were administered meloxicam once in accordance with a 2 x 2 crossover design (IV or PO drug administration; horses fed or not fed). The second phase used a multiple-dose regimen (daily oral administration of meloxicam for 14 days), with meloxicam administered at the recommended dosage (0.6 mg/kg). Plasma and urine concentrations of meloxicam were measured by use of validated methods with a limit of quantification of 10 ng/mL for plasma and 20 ng/mL for urine. RESULTS: Plasma clearance was low (mean +/- SD; 34 +/- 0.5 mL/kg/h), steady-state volume of distribution was limited (0.12 +/- 0.018 L/kg), and terminal half-life was 8.54 +/- 3.02 hours. After oral administration, bioavailability was nearly total regardless of feeding status (98 +/- 12% in fed horses and 85 +/- 19% in nonfed horses). During once-daily administration for 14 days, we did not detect drug accumulation in the plasma. Meloxicam was eliminated via the urine with a urine-to-plasma concentration that ranged from 13 to 18. Concentrations were detected for a relatively short period (3 days) after administration of the final daily dose. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study support once-daily administration of meloxicam regardless of the feeding status of a horse and suggest a period of at least 3 days before urine concentrations of meloxicam reach concentrations that could be used in drug control programs.  相似文献   

6.
OBJECTIVE: To quantitate the dose- and time-related effects of IV administration of xylazine and detomidine on urine characteristics in horses deprived of feed and water. ANIMALS: 6 horses. PROCEDURE: Feed and water were withheld for 24 hours followed by i.v. administration of saline (0.9% NaCI) solution, xylazine (0.5 or 1.0 mg/kg), or detomidine (0.03 mg/kg). Horses were treated 4 times, each time with a different protocol. Following treatment, urine and blood samples were obtained at 15, 30, 60, 120, and 180 minutes. Blood samples were analyzed for PCV and serum concentrations of total plasma solids, sodium, and potassium. Urine samples were analyzed for pH and concentrations of glucose, proteins, sodium, and potassium. RESULTS: Baseline (before treatment) urine flow was 0.30 +/- 0.03 mL/kg/h and did not significantly change after treatment with saline solution and low-dose xylazine but transiently increased by 1 hour after treatment with high-dose xylazine or detomidine. Total urine output at 2 hours following treatment was 312 +/- 101 mL versus 4,845 +/- 272 mL for saline solution and detomidine, respectively. Absolute values of urine concentrations of sodium and potassium also variably increased following xylazine and detomidine administration. CONCLUSIONS AND CLINICAL RELEVANCE: Xylazine and detomidine administration in horses deprived of feed and water causes transient increases in urine volume and loss of sodium and potassium. Increase in urine flow is directly related to dose and type of alpha2-adrenergic receptor agonist. Dehydration in horses may be exacerbated by concurrent administration of alpha2-adrenergic receptor agonists.  相似文献   

7.
The pharmacokinetics of a multidose regimen of potassium bromide (KBr) administration in normal dogs was examined. KBr was administered at 30 mg/kg p.o. q 12 h for a period of 115 days. Serum, urine, and cerebrospinal fluid (CSF) bromide (BR) concentrations were measured at the onset of dosing, during the accumulation phase, at steady-state, and after a subsequent dose adjustment. Median elimination half-life and steady-state serum concentration were 15.2 days and 245 mg/dL, respectively. Apparent total body clearance was 16.4 mL/day/kg and volume of distribution was 0.40 L/kg. The CSF:serum BR ratio at steady-state was 0.77. Dogs showed no neurologic deficits during maintenance dosing but significant latency shifts in waves I and V of the brainstem auditory evoked response were evident. Following a subsequent dose adjustment, serum BR concentrations of approximately 400 mg/dL were associated with caudal paresis in two dogs. Estimated half-life during the accumulation phase was shorter than elimination half-lives reported in other studies and was likely related to dietary chloride content. The range of steady-state concentrations achieved suggests individual differences in clearance and bioavailability between dogs. The described protocol reliably produced serum BR concentrations that are required by many epileptic patients for satisfactory seizure control.  相似文献   

8.
OBJECTIVE: To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses. ANIMALS: 11 healthy adult horses. PROCEDURE: Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured. RESULTS: Mean +/- SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 +/- 0.37 microg/mL, 2.35 +/- 0.78 microg/mL, and 2.40 +/- 0.29 microg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean +/- SD voriconazole concentration in AH after a single orally administered dose was 0.86 +/- 0.22 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.  相似文献   

9.
OBJECTIVE: To compare the disposition of lidocaine administered IV in awake and anesthetized horses. ANIMALS: 16 horses. PROCEDURE: After instrumentation and collection of baseline data, lidocaine (loading infusion, 1.3 mg/kg administered during 15 minutes (87 microg/kg/min); constant rate infusion, 50 microg/kg/min) was administered IV to awake or anesthetized horses for a total of 105 minutes. Blood samples were collected at fixed times during the loading and maintenance infusion periods and after the infusion period for analysis of serum lidocaine concentrations by use of liquid chromatography with mass spectral detection. Selected cardiopulmonary parameters including heart rate (HR), mean arterial pressure (MAP), arterial pH, PaCO2, and PaO2 were also recorded at fixed time points during lidocaine administration. Serum lidocaine concentrations were evaluated by use of standard noncompartmental analysis. RESULTS: Serum lidocaine concentrations were higher in anesthetized than awake horses at all time points during lidocaine administration. Serum lidocaine concentrations reached peak values during the loading infusion in both groups (1,849 +/- 385 ng/mL and 3,348 +/- 602 ng/mL in awake and anesthetized horses, respectively). Most lidocaine pharmacokinetic variables also differed between groups. Differences in cardiopulmonary variables were predictable; for example, HR and MAP were lower and PaO2 was higher in anesthetized than awake horses but within reference ranges reported for horses under similar conditions. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthesia has an influence on the disposition of lidocaine in horses, and a change in dosing during anesthesia should be considered.  相似文献   

10.
OBJECTIVES: To determine the disposition of orally administered cefpodoxime proxetil in foals and adult horses and measure the minimum inhibitory concentrations (MICs) of the drug against common bacterial pathogens of horses. ANIMALS: 6 healthy adult horses and 6 healthy foals at 7 to 14 days of age and again at 3 to 4 months of age. PROCEDURE: A single dose of cefpodoxime proxetil oral suspension was administered (10 mg/kg) to each horse by use of a nasogastric tube. In 7- to 14-day-old foals, 5 additional doses were administered intragastrically at 12-hour intervals. The MIC of cefpodoxime for each of 173 bacterial isolates was determined by use of a commercially available test. RESULTS: In 7- to 14-day-old foals, mean +/- SD time to peak serum concentration (Tmax) was 1.7 +/- 0.7 hours, maximum serum concentration (Cmax) was 0.81 +/- 0.22 microg/mL, and elimination half-life (harmonic mean) was 7.2 hours. Disposition of cefpodoxime in 3- to 4-month-old foals was not significantly different from that of neonates. Adult horses had significantly higher Cmax and significantly lower Tmax, compared with values for foals. The MIC of cefpodoxime required to inhibit growth of 90% of isolates for Salmonella enterica, Escherichia coli, Pasteurella spp, Klebsiella spp, and beta-hemolytic streptococci was 0.38, 1.00, 0.16, 0.19, and 0.09 microg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration at a dosage of 10 mg/kg every 6 to 12 hours would appear appropriate for the treatment of equine neonates with bacterial infections.  相似文献   

11.
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   

12.
OBJECTIVE: To determine pharmacokinetics of single and multiple doses of rimantadine hydrochloride in horses and to evaluate prophylactic efficacy of rimantadine in influenza virus-infected horses. ANIMALS: 5 clinically normal horses and 8 horses seronegative to influenza A. PROCEDURE: Horses were given rimantadine (7 mg/kg of body weight, i.v., once; 15 mg/kg, p.o., once; 30 mg/kg, p.o., once; and 30 mg/kg, p.o., q 12 h for 4 days) to determine disposition kinetics. Efficacy in induced infections was determined in horses seronegative to influenza virus A2. Rimantadine was administered (30 mg/kg, p.o., q 12 h for 7 days) beginning 12 hours before challenge-exposure to the virus. RESULTS: Estimated mean peak plasma concentration of rimantadine after i.v. administration was 2.0 micrograms/ml, volume of distribution (mean +/- SD) at steady-state (Vdss) was 7.1 +/- 1.7 L/kg, plasma clearance after i.v. administration was 51 +/- 7 ml/min/kg, and beta-phase half-life was 2.0 +/- 0.4 hours. Oral administration of 15 mg of rimantadine/kg yielded peak plasma concentrations of < 50 ng/ml after 3 hours; a single oral administration of 30 mg/kg yielded mean peak plasma concentrations of 500 ng/ml with mean bioavailability (F) of 25%, beta-phase half-life of 2.2 +/- 0.3 hours, and clearance of 340 +/- 255 ml/min/kg. Multiple doses of rimantadine provided steady-state concentrations in plasma with peak and trough concentrations (mean +/- SEM) of 811 +/- 97 and 161 +/- 12 ng/ml, respectively. Rimantadine used prophylactically for induced influenza virus A2 infection was associated with significant decreases in rectal temperature and lung sounds. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of rimantadine to horses can safely ameliorate clinical signs of influenza virus infection.  相似文献   

13.
OBJECTIVE: To determine the pharmacokinetics of tilmicosin after oral administration of a single dose of tilmicosin base in swine. ANIMALS: 10 healthy swine. PROCEDURE: Tilmicosin base was administered via stomach tube at a single dose of 20 mg/kg (n = 5) or 40 mg/kg (5). Blood samples were obtained from a jugular vein immediately before and at 10, 20, and 30 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours after administration of tilmicosin. Tilmicosin concentrations in serum were quantified by use of a high-performance liquid chromatography procedure with UV light. Data for tilmicosin concentrations versus time were analyzed by use of compartmental and noncompartmental methods. RESULTS: Tilmicosin concentrations in serum decreased in a biexponential manner after oral administration. Mean +/- SD values for absorption half-lives were 1.49 +/- 0.23 hours and 1.64 +/- 0.40 hours, distribution half-lives were 2.96 +/- 0.58 hours and 3.20 +/- 0.76 hours, elimination half-lives were 25.26 +/- 8.25 and 20.69 +/- 5.07 hours, peak concentrations were 1.19 +/- 0.30 microg/mL and 2.03 +/- 0.28 microg/mL, and time to peak concentrations was 3.12 +/- 0.50 hours and 3.48 +/- 0.77 hours after oral administration of tilmicosin base at a single dose of 20 or 40 mg/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In swine, tilmicosin was rapidly absorbed and slowly eliminated after oral administration of a single dose of tilmicosin base powder.  相似文献   

14.
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   

15.
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   

16.
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   

17.
OBJECTIVE: To determine the effect of oral administration of dantrolene sodium on serum creatine kinase (CK) activity after exercise in horses with recurrent exertional rhabdomyolysis (RER). ANIMALS: 2 healthy horses and 5 Thoroughbreds with RER. PROCEDURE: 3 horses received 2 doses of dantrolene (4, 6, or 8 mg/kg, p.o., with and without withdrawal of food) 2 days apart; 90 minutes after dosing, plasma dantrolene concentration was measured spectrofluorometrically. On the basis of these results, 5 Thoroughbreds with RER from which food was withheld received dantrolene (4 mg/kg) or an inert treatment (water [20 mL]) orally 90 minutes before treadmill exercise (30 minutes, 5 d/wk) during two 3-week periods. Serum CK activity was determined 4 hours after exercise. Plasma dantrolene concentration was measured before and 90 minutes after dosing on the first and last days of dantrolene treatment and before dosing on the first day of the inert treatment period, RESULTS: 90 minutes after dosing, mean +/- SEM plasma dantrolene concentration was 0.62 +/- 0.13 and 0 microg/mL in the dantrolene and inert treatment groups, respectively. Serum CK activity was lower in dantrolene-treated horses (264 +/- 13 U/L), compared with activity in water-treated horses (1,088 +/- 264 U/L). Two horses displayed marked muscle stiffness on the inert treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In 5 horses with RER from which food had been withheld, 4 mg of dantrolene/kg administered orally provided measurable, though variable, plasma concentrations and significantly decreased serum CK activity after exercise in 4 of those horses.  相似文献   

18.
OBJECTIVE: To determine serum pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite in horses after administration of a single IV dose and after single and multiple oral doses. ANIMALS: 8 healthy adult horses. PROCEDURES: A crossover study design was used with a washout period of 6 days between treatments. Treatments were IV administration of a single dose of pentoxifylline (8.5 mg/kg) and oral administration of generic sustained-release pentoxifylline (10 mg/kg, q 12 h, for 8 days). Blood samples were collected 0, 1, 3, 6, 12, 20, 30, and 45 minutes and 1, 2, 4, 6, 8, and 12 hours after IV administration. For oral administration, blood samples were collected 0, 0.25, 0.5, 0.75, 1, 2, 4, 8, and 12 hours after the first dose and 0, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, and 24 hours after the last dose. RESULTS: Elimination of pentoxifylline was rapid after IV administration. After oral administration, pentoxifylline was rapidly absorbed and variably eliminated. Higher serum concentrations of pentoxifylline and apparent bioavailability were observed after oral administration of the first dose, compared with values after administration of the last dose on day 8 of treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, oral administration of 10 mg of pentoxifylline/kg results in serum concentrations equivalent to those observed for therapeutic doses of pentoxifylline in humans. Twice daily administration appears to be appropriate. However, serum concentrations of pentoxifylline appear to decrease with repeated dosing; thus, practitioners may consider increasing the dosage if clinical response diminishes with repeated administration.  相似文献   

19.
OBJECTIVE: To determine pharmacokinetics, safety, and penetration into interstitial fluid (ISF), polymorphonuclear leukocytes (PMNLs), and aqueous humor of doxycycline after oral administration of single and multiple doses in horses. ANIMALS: 6 adult horses. PROCEDURE: The effect of feeding on drug absorption was determined. Plasma samples were obtained after administration of single or multiple doses of doxycycline (20 mg/kg) via nasogastric tube. Additionally, ISF, PMNLs, and aqueous humor samples were obtained after the final administration. Horses were monitored for adverse reactions. RESULTS: Feeding decreased drug absorption. After multiple doses, mean +/- SD time to maximum concentration was 1.63 +/- 1.36 hours, maximum concentration was 1.74 +/- 0.3 microg/mL, and elimination half-life was 12.07 +/- 3.17 hours. Plasma protein binding was 81.76 +/- 2.43%. The ISF concentrations correlated with the calculated percentage of non-protein-bound drug. Maximum concentration was 17.27 +/- 8.98 times as great in PMNLs, compared with plasma. Drug was detected in aqueous humor at 7.5% to 10% of plasma concentrations. One horse developed signs of acute colitis and required euthanasia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that doxycycline administered at a dosage of 20 mg/kg, PO, every 24 hours will result in drug concentrations adequate for killing intracellular bacteria and bacteria with minimum inhibitory concentration < or = 0.25 microg/mL. For bacteria with minimum inhibitory concentration of 0.5 to 1.0 microg/mL, a dosage of 20 mg/kg, PO, every 12 hours may be required; extreme caution should be exercised with the higher dosage until more safety data are available.  相似文献   

20.
The purpose of the study reported here was to describe the bioavailability and pharmacokinetics of acyclovir after intravenous and oral administration to horses. Six healthy adult horses were used in a randomized cross-over study with a 3 x 3 Latin square design. Three treatments were administered to each horse: 10 mg of injectable acyclovir/kg of body weight in 1 L of normal saline delivered as an infusion over 15 minutes; 10 mg of acyclovir/kg in tablets by nasogastric intubation; and 20 mg of acyclovir/kg in tablets by nasogastric intubation. A 2-week washout period was provided between each treatment. Serum samples were obtained for acyclovir assay using reversed-phase, high-performance liquid chromatography with fluorescence detection. Deproteinated serum was injected onto a C18 column, and elution occurred under isocratic conditions. The limit of quantification was 0.04 microg/mL. The assay exhibited suitable accuracy, precision, and recovery. The IV data were analyzed by a 3-compartment model, and oral data were analyzed noncompartmentally. Intragastric acyclovir administration at either dose was associated with high variability in serum acyclovir-time profiles, low Cmax, and poor bioavailability. The dosage of 20 mg/kg was associated with mean (+/- SD) Cmax of 0.19 +/- 0.10 microg/mL, and bioavailability was 2.8%. Inhibition of equine herpesvirus has been reported to require significantly higher acyclovir concentrations than those obtained here. The results of this study do not support a therapeutic benefit for the oral administration of acyclovir up to doses of 20 mg/kg.  相似文献   

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