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1.
Pharmacokinetics of topically applied ciprofloxacin in equine tears   总被引：1，自引：1，他引：0  
OBJECTIVE: To evaluate the pharmacokinetics of topically applied ciprofloxacin 0.3% ophthalmic solution in tears of healthy horses. ANIMAL STUDIED: Twenty healthy, adult, mixed-breed horses. PROCEDURES: Twenty study horses were confirmed free of ophthalmic disease by complete ophthalmic examination. Seventy microliters of 0.3% ciprofloxacin (Ciloxan) was placed in the ventral cul-de-sac of each eye using a microliter syringe and 19-g cannula. Population kinetics were carried out by sampling the tear film from the lower cul-de-sac of each eye with tear test strips at 5, 10, 15 and 30 min and 1, 2, 4 and 6 h post administration for a total of five samples at each time-point. Sample collection time was 15 s. Concentrations of ciprofloxacin were determined using high performance liquid chromatography. RESULTS: Mean (+/-SD) of the Schirmer tear test results from all eyes was 23.4 +/- 4.8 mm wetting in 1 min. Mean concentration of ciprofloxacin in the tears at 5 min post administration was 498.4 +/- 266.8 microg/g. Mean concentration rapidly declined and began to plateau at 30 min. The mean tear concentrations of ciprofloxacin at 30 min and at 1, 2, 4 and 6 h were 66.6 +/- 56.0, 60.25 +/- 55.7, 42.25 +/- 30.9, 36.25 +/- 32.0, and 45.5 +/- 46.5 microg/g, respectively. CONCLUSIONS: The pharmacokinetics of ciprofloxacin in normal horses are similar to those in rabbits and humans. Topical application of ciprofloxacin resulted in a mean tear concentration of ciprofloxacin that remained above the MIC(90) levels for most pathogenic bacteria for 6 h post administration.  相似文献   

2.
The aim of this retrospective study was to determine the frequency of pharyngeal collapse in a large group of brachycephalic dogs undergoing videofluoroscopic assessment of swallowing or airway diameter. We hypothesized that brachycephalic dogs would have pharyngeal collapse more frequently than dolichocephalic or mesocephalic dogs with or without airway collapse. The medical records database was searched for brachycephalic dogs undergoing videofluoroscopy of swallowing or airway diameter between January 1, 2006 and December 31, 2015. A cohort of dolichocephalic/mesocephalic dogs with videofluoroscopically confirmed airway collapse was age and time matched for comparison. A control group of dolichocephalic/mesocephalic dogs that did not have documented airway collapse was also evaluated. All fluoroscopic studies were assessed by a board certified veterinary radiologist for the presence and degree of pharyngeal collapse. Results demonstrate that pharyngeal collapse was significantly more common in brachycephalic dogs (58/82; 72%) than in nonbrachycephalic dogs with (7/25; 28%) and without (2/30; 7%) airway collapse. Pharyngeal collapse is more prevalent in brachycephalic dogs undergoing videofluoroscopy than in dolichocephalic/mesocephalic dogs with or without airway collapse.  相似文献   

3.
Analysis of tear uptake by the Schirmer tear test strip in the canine eye   总被引：1，自引：1，他引：0  
OBJECTIVE: To analyze the uptake of tears in a Schirmer tear test (STT) in vitro and in vitro. MATERIALS AND METHODS: Uptake of fluid by Schirmer tear test strips was studied in vitro by examining fluid uptake over time from an unlimited fluid supply as well as with specific fluid volumes applied to the test strip. Uptake of fluid by Schirmer tear test strips was evaluated in a population of 100 ophthalmologically normal dogs together with a group of 40 dogs with tear film abnormalities such as keratoconjunctivitis sicca (KCS) or epiphora. Each animal was given a full ophthalmic examination followed by a standard Schirmer tear test extended over between 3 and 5 min with the STT reading recorded every 5 s and plotted over time. To determine the effect of ocular irritation by the test strip, uptake of tears by test strips was determined before and after topical anesthesia in 20 dogs. RESULTS: In vitro examination of fluid uptake by the STT strips showed an initial rapid uptake followed by a gradual reduction in rate of uptake. Temporal evaluation of STT in vivo showed a similar rapid initial uptake of tear fluid, followed in the majority of cases by a sudden change to a steady state uptake of fluid. The initial gradient was 29.3 +/- 16.9 mm/min followed by a steady state uptake of 5.2 +/- 2.3 mm/min in normal dogs and 1.9 +/- 1.3 mm/min in dogs with KCS. This corresponds to a steady state tear turnover of 7.8 +/- 3.4 microL/min in normal dogs and 2.8 +/- 1.9 microL/min in animals with KCS. Dogs with nasolacrimal blockage and resultant epiphora showed a high initial gradient but final gradients were not statistically different from those of normal dogs. Discussion and conclusions Temporal evaluation of tear uptake by the STT shows substantial differences in rate of tear uptake at different time-points during the period of the test. RESULTS: of this study suggest that the initial rapid rise in STT value represents uptake from the tear lake followed by a slower tear uptake of tears from steady state tear production. Temporal examination of the Schirmer tear test allows a more precise evaluation of tear production than the standard STT measuring tear uptake in 1 min, together with estimation of the contribution to the test strip tear uptake of tears from the residual tear lake volume and those from continual tear production.  相似文献   

4.
OBJECTIVE: To determine concentrations of marbofloxacin in alveolar macrophages (AMs) and epithelial lining fluid (ELF) and compare those concentrations with plasma concentrations in healthy dogs. ANIMALS: 12 adult mixed-breed and purebred hounds. PROCEDURE: 10 dogs received orally administered marbofloxacin at a dosage of 2.75 mg/kg every 24 hours for 5 days. Two dogs served as nontreated controls. Fiberoptic bronchoscopy and bronchoalveolar lavage procedures were performed while dogs were anesthetized with propofol, approximately 6 hours after the fifth dose. The concentrations of marbofloxacin in plasma and bronchoalveolar fluid (cell and supernatant fractions) were determined by use of high-performance liquid chromatography with detection of fluorescence. RESULTS: Mean +/- SD plasma marbofloxacin concentrations 2 and 6 hours after the fifth dose were 2.36 +/- 0.52 microg/mL and 1.81 +/- 0.21 microg/mL, respectively. Mean +/- SD marbofloxacin concentration 6 hours after the fifth dose in AMs (37.43 +/- 24.61 microg/mL) was significantly greater than that in plasma (1.81 +/- 0.21 microg/mL) and ELF (0.82 +/- 0.34 microg/mL), resulting in a mean AM concentration-to-plasma concentration ratio of 20.4, a mean AM:ELF ratio of 60.8, and a mean ELF-to-plasma ratio of 0.46. Marbofloxacin was not detected in any samples from control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Marbofloxacin concentrations in AMs were greater than the mean inhibitory concentrations of major bacterial pathogens in dogs. Results indicated that marbofloxacin accumulates in AMs at concentrations exceeding those reached in plasma and ELF The accumulation of marbofloxacin in AMs may facilitate treatment for susceptible intracellular pathogens or infections associated with pulmonary macrophage infiltration.  相似文献   

5.
Concentration of total proteins was measured and sodium dodecyl sulfate-polyacrylamide gel disk electrophoresis was performed on tear and plasma samples obtained from 26 healthy dogs, and the results were compared. Mean +/- SEM concentration of total proteins in tears was 0.63 +/- 0.04 g/dl, and significant effects of age or gender were not found. The protein composition of tears in dogs was complex, and bands from light and heavy chains of immunoglobulins were identified by electrophoresis.  相似文献   

6.
The pharmacokinetic behaviour of enrofloxacin in greater rheas was investigated after intramuscular (IM) administration of 15 mg/kg. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by high performance liquid chromatography. Enrofloxacin peak plasma concentration (C(max)=3.30+/-0.90 microg/mL) was reached at 24.17+/-9.17 min. The terminal half-life (t(1/2lambda)) and area under the curve (AUC) were 2.85+/-0.54 h and 4.18+/-0.69 microg h/mL, respectively. The AUC and C(max) for ciprofloxacin were 0.25+/-0.06 microg/mL and 0.66+/-0.16 microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, an IM dose of 15 mg/kg of enrofloxacin would appear to be adequate for treating infections caused by highly susceptible bacteria (MIC(90)<0.03 microg/mL) in greater rheas.  相似文献   

7.
OBJECTIVE: To determine the effect of 6 plasma ketamine concentrations on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS: 6 dogs. PROCEDURE: In experiment 1, the MAC of isoflurane was measured in each dog and the pharmacokinetics of ketamine were determined in isoflurane-anesthetized dogs after IV administration of a bolus (3 mg/kg) of ketamine. In experiment 2, the same dogs were anesthetized with isoflurane in oxygen. A target-controlled IV infusion device was used to administer ketamine and to achieve plasma ketamine concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL by use of parameters obtained from experiment 1. The MAC of isoflurane was determined at each plasma ketamine concentration, and blood samples were collected for ketamine and norketamine concentration determination. RESULTS: Actual mean +/- SD plasma ketamine concentrations were 1.07 +/- 0.42 microg/mL, 1.62 +/- 0.98 microg/mL, 3.32 +/- 0.59 microg/mL, 4.92 +/- 2.64 microg/mL, 13.03 +/- 10.49 microg/mL, and 22.80 +/- 25.56 microg/mL for target plasma concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL, respectively. At these plasma concentrations, isoflurane MAC was reduced by 10.89% to 39.48%, 26.77% to 43.74%, 25.24% to 84.89%, 44.34% to 78.16%, 69.62% to 92.31%, and 71.97% to 95.42%, respectively. The reduction in isoflurane MAC was significant, and the response had a linear and quadratic component. Salivation, regurgitation, mydriasis, increased body temperature, and spontaneous movements were some of the adverse effects associated with the high plasma ketamine concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine appears to have a potential role for balanced anesthesia in dogs.  相似文献   

8.
The purpose of this study was to establish the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in the plasma and interstitial fluid (ISF) following subcutaneous (s.c.) administration of enrofloxacin. Ultrafiltration probes were placed in the s.c. tissue, gluteal musculature, and pleural space of five calves. Each calf received 12.5 mg/kg of enrofloxacin. Plasma and ISF samples were collected for 48 h after drug administration and analyzed by high pressure liquid chromatography. Plasma protein binding of enrofloxacin and ciprofloxacin was measured using a microcentrifugation system. Tissue probes were well tolerated and reliably produced fluid from each site. The mean +/- SD plasma half-life was 6.8 +/- 1.2 and 7.3 +/- 1 h for enrofloxacin and ciprofloxacin, respectively. The combined (ciprofloxacin + enrofloxacin) peak plasma concentration (Cmax) was 1.52 microg/mL, and the combined area under the curve (AUC) was 25.33 microg/mL. The plasma free drug concentrations were 54% and 81% for enrofloxacin and ciprofloxacin, respectively, and free drug concentration in the tissue fluid was higher than in plasma. We concluded that Cmax/MIC and AUC/MIC ratios for free drug concentrations in plasma and ISF would meet suggested ratios for a targeted MIC of 0.06 microg/mL.  相似文献   

9.
OBJECTIVE: The objectives of this study were to document the development of axial globe length (AGL) in normal mesocephalic cross-bred dogs between 2 and 52 weeks of age, to determine a relationship between AGL and age, and derive an equation to predict AGL in normal mesocephalic cross-bred dogs. ANIMALS STUDIED AND PROCEDURE: The AGL of twenty normal mesocephalic cross-bred dogs was measured at 12 time points from 2 to 52 weeks of age using B-scan ultrasonography. RESULTS: The mean (+/- SEM) AGL increased from 12.65 mm (+/- 0.18) at 2 weeks of age to 19.52 mm (+/- 0.18) at 52 weeks of age. The correlation between AGL and age was evaluated by fitting possible variables to a regression pattern. A linear model of natural logarithmic-transformed value of AGL (mm) and age (week) was established. Side (left or right eye) and gender did not correlate with development of AGL. CONCLUSIONS: A reverse transformation of the formula can be used to predict AGL in mesocephalic cross-bred dogs: AGL = 10.847 * age in weeks 0.1653.  相似文献   

10.
OBJECTIVE: To determine the relationship between bispectral index (BIS) and minimum alveolar concentration (MAC) multiples of isoflurane after IM injection of medetomidine or saline (0.9% NaCl) solution in anesthetized dogs. ANIMALS: 6 dogs. PROCEDURE: Each dog was anesthetized 3 times with isoflurane. First, the MAC of isoflurane for each dog was determined by use of the tail clamp method. Second, anesthetized dogs were randomly assigned to receive an IM injection of medetomidine (8 microg x kg(-1)) or an equal volume of isotonic saline (0.9% NaCl) solution 30 minutes prior to beginning BIS measurements. Last, anesthetized dogs received the remaining treatment (medetomidine or isotonic saline solution). Dogs were anesthetized at each of 4 MAC multiples of isoflurane. Ventilation was controlled and atracurium (0.2 mg/kg followed by 6 microg/kg/min as a continuous infusion, IV) administered. After a 20-minute equilibration period at each MAC multiple of isoflurane, BIS data were collected for 5 minutes and median values of BIS calculated. RESULTS: BIS significantly decreased with increasing MAC multiples of isoflurane over the range of 0.8 to 2.0 MAC. Mean (+/- SD) MAC of isoflurane was 1.3 +/- 0.2%. During isoflurane-saline anesthesia, mean BIS measurements at 0.8, 1.0, 1.5, and 2.0 MAC were 65 +/- 8, 60 +/- 7 52 +/- 3, and 31 +/- 28, respectively. During isoflurane-medetomidine anesthesia, mean BIS measurements at 0.8, 1.0, 1.5, and 2.0 MAC were 77 +/- 4, 53 +/- 7, 31 +/- 24, and 9 +/- 20, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: BIS monitoring in dogs anesthetized with isoflurane has a predictive value in regard to degree of CNS depression. During isoflurane anesthesia, our results support a MAC-reducing effect of medetomidine.  相似文献   

11.
OBJECTIVE: To compare in vitro and in vivo absorptive capacities of modified Schirmer tear test strips with those of original strips, and to establish reference values for use with the modified strips. DESIGN: Prospective study. ANIMALS: 100 dogs. PROCEDURE: In vitro absorptive capacity was determined by immersing strips in an irrigating solution for 15 seconds and recording amount of wetting. In vivo absorptive capacity was determined by placing an original Schirmer tear test strip in 1 eye and a modified strip in the other eye of 50 dogs with normal or abnormal tear production. Time required to wet 10 mm of each strip was recorded. Measurements were repeated 30 minutes later after reversing which strip was placed in the left or right eye. Reference values (mean +/- SD) were determined by recording the time required to wet 10 mm of the modified strip in 50 healthy dogs. RESULTS: Amount of wetting was significantly less and time required to wet 10 mm was significantly greater for the modified strip, compared with the original strip. Reference values determined for the modified strip were 32 +/- 11 seconds in the right eye, 33 +/- 11 seconds in the left eye, and 32 +/- 10 seconds in both eyes. CONCLUSIONS AND CLINICAL RELEVANCE: Absorptive capacities of the original and modified Schirmer tear test strips were significantly different. Reference values determined for 1 strip should not be used for the other strip.  相似文献   

12.
The amplitude and frequency of growth hormone (GH) secretory pulses are influenced by a variety of hormonal signals, among which glucocorticoids play an important role. The aim of this study was to investigate the pulsatile secretion pattern of GH in dogs in which the endogenous secretion of glucocorticoids is persistently elevated, i.e. in dogs with pituitary-dependent hyperadrenocorticism (PDH). Blood samples for the determination of the pulsatile secretion pattern of GH were collected at 10-min interval between 08:00 and 14:00 h in 16 dogs with PDH and in 6 healthy control dogs of comparable age. The pulsatile secretion patterns of GH were analyzed using the Pulsar program. GH was secreted in a pulsatile fashion in both dogs with PDH and control dogs. There was no statistical difference between the mean (+/-S.E.M.) basal GH level in dogs with PDH (0.7+/-0.1 microg/l) and the control dogs (0.6+/-0.1 microg/l). The mean area under the curve (AUC) for GH above the zero-level in dogs with PDH (4.6+/-0.6 microg/l per 6 h) was significantly lower than that in the control dogs (7.3+/-1.0 microg/l per 6 h). Likewise, the mean AUC for GH above the base-level in dogs with PDH (0.6+/-0.1 microg/l per 6 h) was significantly lower than that in the control dogs (3.7+/-1.0 microg/l per 6 h). The median GH pulse frequency in the dogs with PDH (2 pulses/6 h, range 0-7 pulses/6 h) was significantly lower (P = 0.04) than that (5 pulses/6 h, range 3-9 pulses/6 h) in the control group. The results of this study demonstrate that PDH in dogs is associated with less GH secreted in pulses than in control dogs, whereas the basal plasma GH concentrations were similarly low in both groups. It is discussed that the impaired pulsatile GH secretion in dogs with PDH is the result of alterations in function of pituitary somatotrophs and changes in supra-pituitary regulation.  相似文献   

13.
OBJECTIVE: To assess duration of actions of butorphanol, medetomidine, and a butorphanol-medetomidine combination in dogs given subanesthetic doses of isoflurane (ISO). ANIMALS: 6 healthy dogs. PROCEDURE: Minimum alveolar concentration (MAC) values for ISO were determined. for each dog. Subsequently, 4 treatments were administered to each dog (saline [0.9% NaCl] solution, butorphanol [0.2 mg/kg of body weight], medetomidine [5.0 microg/kg], and a combination of butorphanol [0.2 mg/kg] and medetomidine [5.0 microg/kg]). All treatments were administered IM to dogs concurrent with isoflurane; treatment order was determined, using a randomized crossover design. Treatments were given at 7-day intervals. After mask induction with ISO and instrumentation with a rectal temperature probe, end-tidal CO2 and anesthetic gas concentrations were analyzed. End-tidal ISO concentration was reduced to 90% MAC for each dog. A tail clamp was applied 15 minutes later. After a positive response, 1 of the treatments was administered. Response to application of the tail clamp was assessed at 15-minute intervals until a positive response again was detected. RESULTS: Duration of nonresponse after administration of saline solution, butorphanol, medetomidine, and butorphanol-medetomidine (mean +/- SD) was 0.0+/-0.0, 1.5+/-1.5, 2.63+/-0.49, and 5.58+/-2.28 hours, respectively. Medetomidine effects were evident significantly longer than those for saline solution, whereas effects for butorphanol-medetomidine were evident significantly longer than for each agent administered alone. CONCLUSION AND CLINICAL RELEVANCE: During ISO-induced anesthesia, administration of medetomidine, but not butorphanol, provides longer and more consistent analgesia than does saline solution, and the combination of butorphanol-medetomidine appears superior to the use of medetomidine or butorphanol alone.  相似文献   

14.
OBJECTIVE: To evaluate clinical characteristics and breeds affected with bacterial keratitis and compare patterns of resistance in bacterial isolates over time in dogs. DESIGN: Retrospective cross-sectional study. ANIMALS: 97 dogs with bacterial keratitis. PROCEDURE: Dogs with bacterial keratitis were identified from teaching hospital medical records at the Universities of Tennessee and Florida during the years 1993 to 2003. Data were collected pertaining to breed, Schirmer tear test results, treatments administered at the time of initial examination, bacterial species isolated, and resistance to selected antimicrobials. RESULTS: 66% of the dogs were brachycephalic, 54% had tear production < 15 mm/min, and 29% were receiving a corticosteroid at the time of initial examination. The most common bacteria isolated were Staphylococcus intermedius (29%), beta-hemolytic Streptococcus spp (17%), and Pseudomonas aeruginosa (21%). Staphylococcus intermedius isolates had limited resistance to certain antimicrobials. More than 80% of beta-hemolytic Streptococcus spp isolates were resistant to neomycin, polymyxin B, and tobramycin. Isolates of P aeruginosa were susceptible to tobramycin and gentamicin and had limited resistance to ciprofloxacin and enrofloxacin. Among bacterial species isolated, there was no evidence of development of antimicrobial resistance over time. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggested that administration of ciprofloxacin or a combination of a first-generation cephalosporin and tobramycin may be used in the treatment of bacterial keratitis while awaiting results of bacterial culture and susceptibility testing. Evidence suggests that current methods of medical management of bacterial keratitis are not associated with increased antimicrobial resistance.  相似文献   

15.
Domestic dogs have become a model organism for studying the extent and consequences of morphological diversity, especially in the skull. It has been demonstrated that Cephalic Index (CI, skull width/skull length) correlates with central concentration of ganglion cells in the retina and with ventral rotation of the cerebral hemispheres. These changes may be reflected in the behavior of breeds with different skulls shapes. This study explored skull variation in the breed groups (n = 7) described by the Australian National Kennel Club to determine if CI differed significantly among the breed groups; groups were expected to differ not least in behavior. The CI of 12 representative dogs (females, n = 6; males, n = 6) of the most popular breeds (n = 80; total n = 960 dogs) were measured. Multivariate analysis of variance was performed to determine CI variance among the breed groups and between previously reported clusters of breeds with similar DNA, which identifies common ancestry. Although CI differed significantly among some breed groups, neither the breed groupings nor the DNA clusters satisfactorily explained all the variance in CI. The results show that breed groupings and genetic clusters only partially explain CI differences. They also suggest that CI is on a continuum and that the definition of three categories of canine skull as dolichocephalic, mesocephalic, and brachycephalic may be overly arbitrary.  相似文献   

16.
Enrofloxacin was administered i.v. to five adult mares at a dose of 5 mg/kg. After administration, blood and endometrial biopsy samples were collected at regular intervals for 24 h. The plasma and tissue samples were analyzed for enrofloxacin and the metabolite ciprofloxacin by high-pressure liquid chromatography. In plasma, enrofloxacin had a terminal half-life (t(1/2)), volume of distribution (area method), and systemic clearance of 6.7 +/- 2.9 h, 1.9 +/- 0.4 L/kg, and 3.7 +/- 1.4 mL/kg/min, respectively. Ciprofloxacin had a maximum plasma concentration (Cmax) of 0.28 +/- 0.09 microg/mL. In endometrial tissue, the enrofloxacin Cmax was 1.7 +/- 0.5 microg/g, and the t(1/2) was 7.8 +/- 3.7 h. Ciprofloxacin Cmax in tissues was 0.15 +/- 0.04 microg/g and the t(1/2) was 5.2 +/- 2.0 h. The tissue:plasma enrofloxacin concentration ratios (w/w:w/v) were 0.175 +/- 0.08 and 0.47 +/- 0.06 for Cmax and AUC, respectively. For ciprofloxacin, these values were 0.55 +/- 0.13 and 0.58 +/- 0.31, respectively. We concluded that plasma concentrations achieved after 5 mg/kg i.v. are high enough to meet surrogate markers for antibacterial activity (Cmax:MIC ratio, and AUC:MIC ratio) considered effective for most susceptible gram-negative bacteria. Endometrial tissue concentrations taken from the mares after dosing showed that enrofloxacin and ciprofloxacin both penetrate this tissue adequately after systemic administration and would attain concentrations high enough in the tissue fluids to treat infections of the endometrium caused by susceptible bacteria.  相似文献   

17.
The pharmacokinetic properties and in vitro potency of nimesulide, a nonsteroidal anti-inflammatory drug (NSAID) were investigated in 8 or 10 dogs after intravenous (i.v.), intramuscular (i.m.) and oral (single and multiple dose) administrations at the nominal dose of 5 mg/kg. After i.v. administration, the plasma clearance was 15.3 +/- 4.2 mL/kg/h, the steady-state volume of distribution was low (0.18 +/- 0.011 L/kg) and the elimination half-life was 8.5 +/- 2.1 h. After i.m. administration, the terminal half-life was 14.0 +/- 5.3 h indicating a slow process of absorption with a maximum plasma concentration (6.1 +/- 1.5 microg/mL) at 10.9 +/- 2.1 h postadministration and the systemic bioavailability was 69 +/- 22%. After oral administration in fasted dogs, the maximal plasma concentration (10.1 +/- 2.7 microg/mL) was observed 6.1 +/- 1.6 h after drug administration, the plasma half-life was 6.2 +/- 1.9 h and the mean bioavailability was 47 +/- 12%. After daily oral administrations for 5 days, the average plasma concentration during the fifth dosage interval was 8.1 +/- 2.9 microg/mL and the overall bioavailability was 58 +/- 16%. The mean accumulation ratio was 1.27 +/- 0.4. In vitro nimesulide inhibitory potencies for cyclooxygenase (COX)-1 and COX-2 isoenzymes were determined using a whole blood assay. Canine clotting blood was used to test for inhibition of COX-1 activity and whole blood stimulated by lipopolysaccharide (LPS) was used to test for inhibition of COX-2 activity. The inhibitory concentration (IC50) for inhibition of COX-2 and COX-1 were 1.6 +/- 0.4 microM (0.49 +/- 0.12 microg/mL) and 20.3 +/- 2.8 microM (6.3 +/- 0.86 microg/mL) giving a nimesulide COX-1/COX-2 ratio of 12.99 +/- 3.41. It was concluded that at the currently recommended dosage regimen (5 mg/kg), the plasma concentration totally inhibits COX-2 and partly inhibits COX-1 isoenzyme.  相似文献   

18.
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   

19.
The pharmacokinetics and bioavailability of trimethoprim-sulfamethoxazole (TMP-SMX) were studied in six healthy male-castrate alpacas (Lama pacos) after intravenous (i.v.) or oral (p.o.) drug administration of 15 mg/kg TMP-SMX using a crossover design with a 2-week washout period. After 90 days one group (n = 3) was given a p.o. dose of 30 mg/kg TMP-SMX and the other group (n = 3) was given a p.o. dose of 60 mg/kg TMP-SMX. After i.v. administration of 15 mg/kg of TMP-SMX the mean initial plasma concentration (C0) was 10.75 +/- 2.12 microg/mL for trimethoprim (TMP) and 158.3 +/- 189.3 microg/mL for sulfamethoxazole (SMX). Elimination half-lives were 0.74 +/- 0.1 h for TMP and 2.2 +/- 0.6 h for SMX. The mean residence times were 1.45 +/- 0.72 h for TMP and 2.8 +/- 0.6 h for SMX. The areas under the respective concentration vs. time curves (AUC) were 2.49 +/- 1.62 microg h/mL for TMP and 124 +/- 60 microg h/mL for SMX. Total clearance (Clt) for TMP was 21.63 +/- 9.85 and 1.90 +/- 0.77 mL/min kg for SMX. The volume of distribution at steady state was 2.32 +/- 1.15 L/kg for TMP and 0.35 +/- 0.09 L/kg for SMX. After intragastric administration of 15, 30 and 60 mg/kg the peak concentration (Cmax) of SMX were 1.9 +/- 0.8, 2.6 +/- 0.4 and 2.8 +/- 0.7 microg/mL, respectively. The AUC was 9.1 +/- 5, 25.9 +/- 3.3 and 39.1 +/- 4.1 microg h/mL, respectively. Based upon these AUC values and correcting for dose, the respective bioavailabilities were 7.7, 10.5 and 7.94%. Trimethoprim was not detected in plasma after intragastric administration. These data demonstrate that therapeutic concentrations of TMP-SMX are not achieved after p.o. administration to alpacas.  相似文献   

20.
OBJECTIVES: To determine pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after a single i.v. and i.m. administration of enrofloxacin and tissue residues after serial daily i.m. administration of enrofloxacin in pigs. ANIMALS: 20 healthy male pigs. PROCEDURE: 8 pigs were used in a crossover design to investigate pharmacokinetics of enrofloxacin after a single i.v. and i.m. administration (2.5 mg/kg of body weight). Twelve pigs were used to study tissue residues; they were given daily doses of enrofloxacin (2.5 mg/kg, i.m. for 3 days). Plasma and tissue concentrations of enrofloxacin and ciprofloxacin were determined. Residues of enrofloxacin and ciprofloxacin were measured in fat, kidney, liver, and muscle. RESULTS: Mean (+/-SD) elimination half-life and mean residence time of enrofloxacin in plasma were 9.64+/-1.49 and 12.77+/-2.15 hours, respectively, after i.v. administration and 12.06+/-0.68 and 17.15+/-1.04 hours, respectively, after i.m. administration. Half-life at alpha phase of enrofloxacin was 0.23+/-0.05 and 1.94+/-0.70 hours for i.v. and i.m. administration, respectively. Maximal plasma concentration was 1.17 +/-0.23 microg/ml, and interval from injection until maximum concentration was 1.81+/-0.23 hours. Renal and hepatic concentrations of enrofloxacin (0.012 to 0.017 microg/g) persisted for 10 days; however, at that time, ciprofloxacin residues were not detected in other tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered i.m. at a dosage of 2.5 mg/kg for 3 successive days, with a withdrawal time of 10 days, resulted in a sum of concentrations of enrofloxacin and ciprofloxacin that were less than the European Union maximal residue limit of 30 ng/g in edible tissues.  相似文献   

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