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1.
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   

2.
OBJECTIVE: To study the pharmacokinetics of difloxacin (5 mg/kg) following IV, IM, and intragastric (IG) administration to healthy horses. ANIMALS: 6 healthy mature horses. PROCEDURES: A crossover study design with 3 phases was used (15-day washout periods between treatments). An injectable formulation of difloxacin (5%) was administered IV and IM in single doses (5 mg/kg); for IG administration, an oral solution was prepared and administered via nasogastric tube. Blood samples were collected before and at intervals after each administration. A high-performance liquid chromatography assay with fluorescence detection was used to determine plasma difloxacin concentrations. Pharmacokinetic parameters of difloxacin were analyzed. Plasma creatine kinase activity was monitored to assess tissue damage. RESULTS: Difloxacin plasma concentration versus time data after IV administration were best described by a 2-compartment open model. The disposition of difloxacin following IM or IG administration was best described by a 1-compartment model. Mean half-life for difloxacin administered IV, IM, and IG was 2.66, 5.72, and 10.75 hours, respectively. Clearance after IV administration was 0.28 L/kg.h. After IM administration, the absolute mean +/- SD bioavailability was 95.81 +/- 3.11% and maximum plasma concentration (Cmax) was 1.48 +/- 0.12 mg/L. After IG administration, the absolute bioavailability was 68.62 +/- 10.60% and Cmax was 0.732 +/- 0.05 mg/L. At 12 hours after IM administration, plasma creatine kinase activity had increased 7-fold, compared with the preinjection value. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that difloxacin is likely to be effective for treating susceptible bacterial infections in horses.  相似文献   

3.
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   

4.
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   

5.
Separate high performance liquid chromatographic methods were developed for thiabendazole (TBZ) and 5-hydroxy thiabendazole (5-OH-TBZ) determination in horse plasma using 1-methyl-2-phenyl benzimidazole (MPBZ) as an internal standard. In both methods TBZ and 5-OH-TBZ were extracted from plasma using organic solvents, injected on to a C-18 column, and eluents monitored by a fluorescence detector. However, mobile phase composition, extraction solvent as well as detector wavelength differed in the two methods. The linear range for TBZ was 0.02 to 0.77 microgram ml-1 while that for 5-OH-TBZ was 0.96 to 8.0 micrograms ml-1. A commercially available TBZ oral suspension was administered to four thoroughbred horses in the following manner: days 1 and 2, 44 mg kg-1; days 4 and 5, 440 mg kg-1. Blood samples were collected during the 24 hours after administration and then analysed for TBZ and 5-OH-TBZ. Half-lives (t1/2), maximum plasma concentrations (Cmax), area under plasma concentration time curves (AUC O-alpha), and relative apparent bioavailability (F), were determined using pharmacokinetic equations. The pharmacokinetic parameters varied in the following manner: 1.16 to 13.63 hours (t1/2), 12 to 131 micrograms ml-1 X hours (AUC O-alpha), 3.33 to 8.90 micrograms ml-1 (Cmax), 1.38 to 0.12 (F) after 44 mg kg-1 and 440 mg kg-1 doses, respectively. The ratios of concentrations of TBZ to 5-OH-TBZ after oral administration of TBZ, were significantly lower for 44 mg kg-1 than 440 mg kg-1 doses.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

6.
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   

7.
OBJECTIVE: To determine the pharmacokinetics of enrofloxacin administered IV and orally to foals. ANIMALS: 5 clinically normal foals. PROCEDURE: A 2-dose cross-over trial with IV and oral administration was performed. Enrofloxacin was administered once IV (5 mg/kg of body weight) to 1-week-old foals, followed by 1 oral administration (10 mg/kg) after a 7-day washout period. Blood samples were collected for 48 hours after the single dose IV and oral administrations and analyzed for plasma enrofloxacin and ciprofloxacin concentrations by use of high-performance liquid chromatography. RESULTS: For IV administration, mean +/- SD total area under the curve (AUC0-infinity) was 48.54 +/- 10.46 microg x h/ml, clearance was 103.72 +/- 0.06 ml/kg/h, half-life (t1/2beta) was 17.10 +/- 0.09 hours, and apparent volume of distribution was 2.49 +/- 0.43 L/kg. For oral administration, AUC0-infinity was 58.47 +/- 16.37 microg x h/ml, t1/2beta was 18.39 +/- 0.06 hours, maximum concentration (Cmax) was 2.12 +/- 00.51 microg/ml, time to Cmax was 2.20 +/- 2.17 hours, mean absorption time was 2.09 +/- 0.51 hours, and bioavailability was 42 +/- 0.42%. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with adult horses given 5 mg of enrofloxacin/kg IV, foals have higher AUC0-infinity, longer t1/2beta, and lower clearance. Concentration of ciprofloxacin was negligible. Using a target Cmax to minimum inhibitory concentration ratio of 1:8 to 1:10, computer modeling suggests that 2.5 to 10 mg of enrofloxacin/kg administered every 24 hours would be effective in foals, depending on minimum inhibitory concentration of the pathogen.  相似文献   

8.
Furosemide is the most common diuretic drug used in horses. Furosemide is routinely administered as IV or IM bolus doses 3-4 times a day. Administration PO is often suggested as an alternative, even though documentation of absorption and efficacy in horses is lacking. This study was carried out in a randomized, crossover design and compared 8-hour urine volume among control horses that received placebo, horses that received furosemide at 1 mg/kg PO, and horses that received furosemide at 1 mg/kg IV. Blood samples for analysis of plasma furosemide concentrations, PCV, and total solids were obtained at specific time points from treated horses. Furosemide concentrations were determined by reversed-phase high-performance liquid chromatography with fluorescent detection. Systemic availability of furosemide PO was poor, erratic, and variable among horses. Median systemic bioavailability was 5.4% (25th percentile, 75th percentile: 3.5, 9.6). Horses that received furosemide IV produced 7.4 L (7.1, 7.7) of urine over the 8-hour period. The maximum plasma concentration of 0.03 microg/mL after administration PO was not sufficient to increase urine volume compared with control horses (1.2 L [1.0, 1.4] PO versus 1.2 L [1.0, 1.4] control). There was a mild decrease in urine specific gravity within 1-2 hours after administration of furosemide PO, and urine specific gravity was significantly lower in horses treated with furosemide PO compared with control horses at the 2-hour time point. Systemic availability of furosemide PO was poor and variable. Furosemide at 1 mg/kg PO did not induce diuresis in horses.  相似文献   

9.
SUMMARY: To determine whether administration of glycerol-containing solutions induces a state of transient hyperhydration in resting euhydrated horses, changes in plasma and urine constituents were measured in four horses for 1 h before and 5 h after nasogastric administration of each of four treatments (Experiment 1). Treatments were applied in a randomized fashion and included: (1) 1.0 g.kg(-)(1)glycerol in 8 L of water (G); (2) 8 L of water (W); (3) 8 L of 0.9% NaCl solution (S); and (4) 1.0 g.kg(-)(1)glycerol in 8 L of 0.9% NaCl solution (GS). In a subsequent study, voluntary water intake was measured hourly for 5 h after nasogastric administration of each treatment (Experiment 2). All treatments produced mild plasma volume expansion ranging from 3.2 to 5.8% in Experiment 1. Administration of glycerol containing solutions increased serum glycerol concentration approximately 100-fold and plasma osmolality (P(osm)) by approximately 10 mOsm/kg and resulted in a tendency towards increased renal water conservation despite increased osmole excretion. In contrast, W treatment decreased plasma and urine osmolality and was accompanied by increased urine production and decreased renal water conservation. Plasma and urine osmolality, as well as renal osmole and water excretion, were unchanged after S administration. In Experiment 2, horses treated with GS voluntarily drank an additional 5.2 +/- 0.9 L of water during the initial hour following nasogastric administration of 8 L of solution. Voluntary water intake with the other treatments was less than 1.0 L for the entire 5 h observation period. Collectively, the results of both experiments suggest that administration of glycerol in saline would produce transient hyperhydration in resting euhydrated horses by enhancing renal water conservation and stimulating voluntary water intake.  相似文献   

10.
Alterations in electrolyte and acid-base balance were studied in 6 horses for 8 hours after furosemide administration (1 mg/kg of body weight, IM), and the results were compared with those for 5 healthy untreated horses (controls) kept under identical environmental conditions. In the treated group, decreases in plasma potassium, chloride, and calcium concentrations and increases in total plasma protein content persisted for the 8-hour observation period, whereas there was no change in plasma sodium concentration, osmolality, or packed cell volume. Plasma bicarbonate concentration and PCO2 remained high throughout the study, during which time venous blood pH was modestly increased only at the 6-hour sampling time. Furosemide treatment resulted in decreases in urine pH, specific gravity, osmolality, and potassium and calcium concentrations and increases in urine volume and total urine sodium, chloride, and calcium excretion. Body weight decreased 19.2 +/- 5.2 kg (mean +/- SD) in treated horses (4 +/- 1% of body weight), compared with a weight loss of 8 +/- 2.1 kg in untreated horses (1.5 +/- 0.4% of body weight) during the 8-hour experimental period. The increased fluid losses induced by the diuretic did not cause any obvious clinical signs in the horses. Pulse pressure, skin turgor, capillary refill time, and jugular distensibility remained unchanged throughout the experimental period.  相似文献   

11.
OBJECTIVE: To characterize pharmacokinetics of voriconazole in horses after oral and IV administration and determine the in vitro physicochemical characteristics of the drug that may affect oral absorption and tissue distribution. ANIMALS: 6 adult horses. PROCEDURES: Horses were administered voriconazole (1 mg/kg, IV, or 4 mg/kg, PO), and plasma concentrations were measured by use of high-performance liquid chromatography. In vitro plasma protein binding and the octanol:water partition coefficient were also assessed. RESULTS: Voriconazole was adequately absorbed after oral administration in horses, with a systemic bioavailability of 135.75 +/- 18.41%. The elimination half-life after a single orally administered dose was 13.11 +/- 2.85 hours, and the maximum plasma concentration was 2.43 +/- 0.4 microg/mL. Plasma protein binding was 31.68%, and the octanol:water partition coefficient was 64.69. No adverse reactions were detected during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Voriconazole has excellent absorption after oral administration and a long half-life in horses. On the basis of the results of this study, it was concluded that administration of voriconazole at a dosage of 4 mg/kg, PO, every 24 hours will attain plasma concentrations adequate for treatment of horses with fungal infections for which the fungi have a minimum inhibitory concentration 相似文献   

12.
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   

13.
OBJECTIVE: To determine the pharmacokinetics of itraconazole after IV or oral administration of a solution or capsules to horses and to examine disposition of itraconazole in the interstitial fluid (ISF), aqueous humor, and polymorphonuclear leukocytes after oral administration of the solution. ANIMALS: 6 healthy horses. PROCEDURE: Horses were administered itraconazole solution (5 mg/kg) by nasogastric tube, and samples of plasma, ISF, aqueous humor, and leukocytes were obtained. Horses were then administered itraconazole capsules (5 mg/kg), and plasma was obtained. Three horses were administered itraconazole (1.5 mg/kg, IV), and plasma samples were obtained. All samples were analyzed by use of high-performance liquid chromatography. Plasma protein binding was determined. Data were analyzed by compartmental and noncompartmental pharmacokinetic methods. RESULTS: Itraconazole reached higher mean +/- SD plasma concentrations after administration of the solution (0.41 +/- 0.13 microg/mL) versus the capsules (0.15 +/- 0.12 microg/mL). Bioavailability after administration of capsules relative to solution was 33.83 +/- 33.08%. Similar to other species, itraconazole has a high volume of distribution (6.3 +/- 0.94 L/kg) and a long half-life (11.3 +/- 2.84 hours). Itraconazole was not detected in the ISF, aqueous humor, or leukocytes. Plasma protein binding was 98.81 +/- 0.17%. CONCLUSIONS AND CLINICAL RELEVANCE: Itraconazole administered orally as a solution had higher, more consistent absorption than orally administered capsules and attained plasma concentrations that are inhibitory against fungi that infect horses. Administration of itraconazole solution (5 mg/kg, PO, q 24 h) is suggested for use in clinical trials to test the efficacy of itraconazole in horses.  相似文献   

14.
OBJECTIVE: To determine the pharmacokinetics of acetazolamide administered IV and orally to horses. ANIMALS: 6 clinically normal adult horses. PROCEDURE: Horses received 2 doses of acetazolamide (4 mg/kg of body weight, IV; 8 mg/kg, PO), and blood samples were collected at regular intervals before and after administration. Samples were assayed for acetazolamide concentration by high-performance liquid chromatography, and concentration-time data were analyzed. RESULTS: After IV administration of acetazolamide, data analysis revealed a median mean residence time of 1.71 +/- 0.90 hours and median total body clearance of 263 +/- 38 ml/kg/h. Median steady-state volume of distribution was 433 +/- 218 ml/kg. After oral administration, mean peak plasma concentration was 1.90 +/- 1.09 microg/ml. Mean time to peak plasma concentration was 1.61 +/- 1.24 hours. Median oral bioavailability was 25 +/- 6%. CONCLUSIONS AND CLINICAL RELEVANCE: Oral pharmacokinetic disposition of acetazolamide in horses was characterized by rapid absorption, low bioavailability, and slower elimination than observed initially after IV administration. Pharmacokinetic data generated by this study should facilitate estimation of appropriate dosages for acetazolamide use in horses with hyperkalemic periodic paralysis.  相似文献   

15.
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   

16.
REASONS FOR PERFORMING STUDY: Danofloxacin is a fluoroquinolone developed for veterinary medicine showing an excellent activity. However, danofloxacin pharmacokinetics profile have not been studied in horses previously. OBJECTIVE: To study the pharmacokinetics following i.v., i.m. and intragastric (i.g.) administration of 1.25 mg/kg bwt danofloxacin to 6 healthy horses. METHODS: A cross-over design was used in 3 phases (2 x 2 x 2), with 2 washout periods of 15 days (n = 6). Danofloxacin (18%) was administered by i.v. and i.m. routes at single doses of 1.25 mg/kg bwt. For i.g. administration an oral solution was prepared and administered via nasogastric tube. Danofloxacin concentrations were determined by HPLC assay with fluorescence detection. Tolerability at the the site of i.m. injection was monitored by creatine kinase (CK) activity. RESULTS: Danofloxacin plasma concentration vs. time data after i.v. and i.g. administration could best be described by a 2-compartment open model. The disposition of i.m. administered danofloxacin was best described by a one-compartment model. The terminal half-lives for i.v., i.m. and i.g. routes were 6.31, 5.36 and 4.74 h, respectively. Clearance value after i.v. dosing was 0.34 l/kg bwt/h. After i.m. administration, absolute bioavailability was mean +/- s.d. 88.48 +/- 11.10% and Cmax was 0.35 +/- 0.05 mg/l. After i.g. administration, absolute bioavailability was 22.36 +/- 6.84% and Cmax 0.21 +/- 0.07 mg/l. CK activity following i.m. dosing increased 3-fold over pre-injection levels 12 h after dosing and subsequently approached (but did not reach) normal values at 72 h post dose. CONCLUSIONS: Systemic danofloxacin exposure achieved in horses following i.m. administration was consistent with the predicted blood levels needed for a positive therapeutic outcome for many equine infections. Conversely, danofloxacin utility by the i.g. route was limited by low bioavailability. Tolerability associated with i.m. administration was high. POTENTIAL RELEVANCE: Pharmacokinetics, blood levels and good tolerability of i.v. and i.m. administration of danofloxacin in horses indicates that it is likely to be effective for treating sensitive bacterial infections.  相似文献   

17.
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18.
OBJECTIVE: To determine the clinical effects and pharmacokinetics of amiodarone after single doses of 5 mg/kg administered orally or intravenously. ANIMALS: 6 healthy adult horses. PROCEDURE: In a cross over study, clinical signs and electrocardiographic variables were monitored and plasma and urine samples were collected. A liquid chromatography-mass spectrometry method was used to determine the percentage of protein binding and to measure plasma and urine concentrations of amiodarone and the active metabolite desethylamiodarone. RESULTS: No adverse clinical signs were observed. After IV administration, median terminal elimination half-lives of amiodarone and desethylamiodarone were 51.1 and 75.3 hours, respectively. Clearance was 0.35 L/kg x h, and the apparent volume of distribution for amiodarone was 31.1 L/kg. The peak plasma desethylamiodarone concentration of 0.08 microg/mL was attained 2.7 hours after IV administration. Neither parent drug nor metabolite was detected in urine, and protein binding of amiodarone was 96%. After oral administration of amiodarone, absorption of amiodarone was slow and variable; bioavailability ranged from 6.0% to 33.7%. The peak plasma amiodarone concentration of 0.14 microg/mL was attained 7.0 hours after oral administration and the peak plasma desethylamiodarone concentration of 0.03 microg/mL was attained 8.0 hours after administration. Median elimination half-lives of amiodarone and desethylamiodarone were 24.1 and 58.6 hours, respectively. CONCLUSION AND CLINICAL RELEVANCE: Results indicate that the pharmacokinetic distribution of amiodarone is multicompartmental. This information is useful for determining treatment regimens for horses with arrythmias. Amiodarone has low bioavailability after oral administration, does not undergo renal excretion, and is highly protein-bound in horses.  相似文献   

19.
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20.
OBJECTIVE: To determine the effectiveness of administering multiple doses of phenylbutazone alone or a combination of phenylbutazone and flunixin meglumine to alleviate lameness in horses. ANIMALS: 29 adult horses with naturally occurring forelimb and hind limb lameness. PROCEDURES: Lameness evaluations were performed by use of kinematic evaluation while horses were trotting on a treadmill. Lameness evaluations were performed before and 12 hours after administration of 2 nonsteroidal anti-inflammatory drug (NSAID) treatment regimens. Phenylbutazone paste was administered at approximately 2.2 mg/kg, PO, every 12 hours for 5 days, or phenylbutazone paste was administered at approximately 2.2 mg/kg, PO, every 12 hours for 5 days in combination with flunixin meglumine administered at 1.1 mg/kg, IV, every 12 hours for 5 days. RESULTS: Alleviation of lameness was greater after administration of the combination of NSAIDs than after oral administration of phenylbutazone alone. Improvement in horses after a combination of NSAIDs did not completely mask lameness. Five horses did not improve after either NSAID treatment regimen. All posttreatment plasma concentrations of NSAIDs were less than those currently allowed by the United States Equestrian Federation Inc for a single NSAID. One horse administered the combination NSAID regimen died of acute necrotizing colitis during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a combination of NSAIDs at the dosages and intervals used in the study reported here alleviated the lameness condition more effectively than did oral administration of phenylbutazone alone. This may attract use of combinations of NSAIDs to increase performance despite potential toxic adverse effects.  相似文献   

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