Effects of doxycycline, amoxicillin, cephalexin, and enrofloxacin on hemostasis in healthy dogs

OBJECTIVE: To determine the effects of enteral administration of doxycycline, amoxicillin, cephalexin, and enrofloxacin at therapeutic dosages for a typical duration on hemostatic variables in healthy dogs. ANIMALS: 14 Beagles. PROCEDURE: Doxycycline (10 mg/kg, PO, q 12 h), amoxicillin (30 mg/kg, PO, q 12 h), cephalexin (30 mg/kg, PO, q 12 h), and enrofloxacin (20 mg/kg, PO, q 24 h) were administered in random order to 10 healthy dogs at standard therapeutic dosages for 7 days, with a 7-day washout period between subsequent antimicrobials. In addition, 4 Beagles served as control dogs. Variables were evaluated before and after antimicrobial administration; they included platelet count, Hct, 1-stage prothrombin time (PT), activated partial thromboplastin time (PTT), fibrinogen concentration, and platelet function. Platelet function was assessed via buccal mucosal bleeding time, aggregation, and a platelet-function analyzer. RESULTS: Administration of all antimicrobials caused a slight prolongation of 1-stage PT and activated PTT and slight decrease in fibrinogen concentration. Cephalexin caused a significant increase in 1-stage PT and activated PTT, amoxicillin caused a significant increase in activated PTT, and enrofloxacin caused a significant decrease in fibrinogen concentration. Platelet count or function did not differ significantly after administration of any antimicrobial. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of commonly used antimicrobials in healthy dogs resulted in minor secondary hemostatic abnormalities, with no change in platelet count or function. Although these changes were clinically irrelevant in healthy dogs, additional studies of the effects of antimicrobial administration on hemostasis in animals with underlying disease processes are warranted.     

恩诺沙星及其代谢物环丙沙星在猪粪便及尿液中的排泄研究

给猪连续3d饲喂含无味恩诺沙星的饲料后，对其排泄的粪便和尿液进行了药物含量测定结果表明，粪便和尿液中恩诺沙星及其代谢产物环丙沙星的排泄量都比较高，粪便中排泄的药物浓度显著高于尿液中药物排泄的浓度，停止给药后第15天，在猪粪中可检测到恩诺沙星，停止给药后第10天，猪尿液中可检测到环丙沙星。     

Pharmacokinetic interactions of flunixin meglumine and enrofloxacin in dogs

OBJECTIVE: To examine pharmacokinetic interactions of flunixin meglumine and enrofloxacin in dogs following simultaneously administered SC injections of these drugs. ANIMALS: 10 Beagles (4 males and 6 females). PROCEDURE: All dogs underwent the following 3 drug administration protocols with a 4-week washout period between treatments: flunixin administration alone (1 mg/kg, SC); simultaneous administration of flunixin (1 mg/kg, SC) and enrofloxacin (5 mg/kg, SC); and enrofloxacin administration alone (5 mg/kg, SC). Blood samples were collected from the cephalic vein at 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12, and 24 hours following SC injections, and pharmacokinetic parameters of flunixin and enrofloxacin were calculated from plasma drug concentrations. RESULTS: Significant increases in the area under the curve (32%) and in the elimination half-life (29%) and a significant decrease (23%) in the elimination rate constant from the central compartment of flunixin were found following coadministration with enrofloxacin, compared with administration of flunixin alone. A significant increase (50%) in the elimination half-life and a significant decrease (21%) in the maximum plasma drug concentration of enrofloxacin were found following coadministration with flunixin, compared with administration of enrofloxacin alone. CONCLUSIONS AND CLINICAL RELEVANCE: The observed decrease in drug clearances as a result of coadministration of flunixin and enrofloxacin indicates that these drugs interact during the elimination phase. Consequently, care should be taken during the concomitant use of flunixin and enrofloxacin in dogs to avoid adverse drug reactions.     

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and oral administration of enrofloxacin in dogs

Rung, K., Riond, J.-L. & Wanner, M. Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and oral administration of enrofloxacin in dogs. J. vet
Four dogs were given 5 mg/kg body weight enrofloxacin intravenously (i.v.) and orally (p.o.) in a cross-over study. Plasma concentrations of the active ingredient enrofloxacin and its main metabolite ciprofloxacin were determined by a reversed phase liquid chromatographic method. Pharmacokinetic parameters of both substances were calculated by use of statistical moments and were compared to those of enrofloxacin described in the veterinary literature. Mean enrofloxacin t _½λZ was 2.4 h, mean Cl_s was 27.1 ml/min-kg, and mean V_ss was 7.0 1/kg. After i.v. and p.o. administration, concentrations of ciprofloxacin exceeding minimal inhibitory concentrations of several microorganisms were reached (C_max= 0.2 ng/ml, max = 2.2 h after intravenous administration; C_max= 0.2 (ig/ml, t _max= 3.6 h after oral administration). A considerable part of the antimicrobial activity is due to ciprofloxacin, the main metabolite of enrofloxacin.     

Pharmacokinetics of two once-daily parenteral cephalexin formulations in dogs

The aims of this study were to describe and compare the pharmacokinetic profiles and T(>MIC90) of two commercially available once-daily recommended cephalexin formulations in healthy adult dogs administered by the intramuscular (i.m.) route. Six beagle dogs received a 10 mg/kg dose of an 18% parenteral suspension of cephalexin of laboratory A (formulation A) and laboratory B (formulation B) 3 weeks apart. Blood samples were collected in predetermined times after drug administration. The main pharmacokinetic parameters were (mean +/- SD): AUC((0-infinity)), 72.44 +/- 15.9 and 60.83 +/- 13.2 microg.h/mL; C(max), 10.11 +/- 1.5 and 8.50 +/- 1.9 microg/mL; terminal half-life, 3.56 +/- 1.5 and 2.57 +/- 0.72 h and MRT((0-infinity)), 5.86 +/- 1.5 and 5.36 +/- 1.2 h for formulations A and B, respectively. T(>MIC90) was 63.1 +/- 14.7 and 62.1 +/- 14.7% of the dosing interval for formulations A and B, respectively. Median (range) for t(max) was 2.0 (2.0-3.0) h and 3.0 (2.0-4.0) for formulations A and B, respectively. Geometric mean ratios of natural log-transformed AUC((0-infinity)) and C(max) and their 90% confidence intervals (CI) were 0.84 (0.72-0.98) and 0.83 (0.64-1.07), respectively. The plasma profiles of cephalexin following the administration of both formulations were similar. No statistical differences between pharmacokinetic parameters or T(>MIC90) were observed, however, bioequivalence between both formulations could not be demonstrated, as lower 90% CI failed to fell within the selected range of 80-125% for bioequivalence.     

Investigation of biochemical and haematological side-effects of enrofloxacin in dogs

In the present study, effects of enrofloxacin on biochemical, haematological and blood gas parameters were investigated. Changes in laboratory parameters were monitored during the treatment period. Enrofloxacin was administered (5 mg/kg intramuscularly, once daily) to 10 healthy dogs for 14 days. Acidosis and temporary increases in aspartate aminotransferase, indirect bilirubin, sodium, partial pressure of CO2 and mean corpuscular volume levels as well as decreased levels of inorganic phosphorus, ionized calcium, potassium, partial pressure of O2 and standard bicarbonate were observed. The results of this study suggest that these observed effects of enrofloxacin on blood gas parameters should be taken into consideration in long-term use of the drug.     

Pharmacokinetics of cephalexin from two oral formulations in dogs

Six beagle dogs were treated with cephalexin-monohydrate from 2 oral formulations (Rilexine tablets and Cefaseptin dragees, respectively) in a dosage of 25 mg/kg and plasma concentrations of cephalexin were measured over 8 hours. After solid phase extraction of the samples, cephalexin was determined by high pressure liquid chromatography with UV detection. After administration, Cephalexin was absorbed rapidly and mean maximum plasma concentrations of 30.9 and 27.9 micrograms/ml, respectively, were acquired after approximately 1.6 hours. Minimal inhibitory concentrations of < or = 6.25 micrograms/ml for in vitro sensitive bacteria were maintained for about 5 hours. Cephalexin from the tested preparations reached a mean area under the plasma concentration-time curve of 115.3 and 102.4 micrograms.h/ml, respectively. The plasma concentration decreased rapidly with a mean half life period of 1.4 hours in average. The other calculated pharmacokinetic parameters were also in the area of the data for dogs stated in the literature. There was no clear difference in the pharmacokinetics of both products, especially the bioavailability. Furthermore, both formulations were well tolerated clinically.     

Investigation of the effect of acepromazine on intravenous glucose tolerance tests in dogs

OBJECTIVE: To investigate the effects of administration of acepromazine on IV glucose tolerance tests (IVGTTs) in dogs. ANIMALS: 8 male mixed-breed dogs. PROCEDURE: With a 1-week interval between tests, each dog underwent (in random order) an IVGTT with or without pretest administration of acepromazine maleate (0.1 mg/kg, SC, 30 minutes prior to the start of the IVGTT). Food was withheld from the dogs for 14 hours prior to each test. Blood samples were obtained at 20, 10, and 1 minute prior to and at 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 19, 22, 25, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, and 180 minutes after administration of glucose. RESULTS: There were no significant differences in the baseline (ie, after food was withheld) plasma glucose, lactate, and insulin concentrations between dogs undergoing the IVGTT and acepromazine-IVGTT; however, lower baseline free fatty acid concentration was observed in acepromazine-treated dogs. Analysis of data via the application of Bergman's minimal model of glucose kinetics revealed no differences in insulin sensitivity, acute insulin response to glucose, disposition index, or glucose effectiveness between dogs treated or not treated with acepromazine before testing. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that in dogs undergoing IV glucose tolerance testing, pretest administration of small doses of acepromazine can be used as a means of chemical restraint without interfering with results of the glucose metabolism assessment.     

A noninferiority clinical trial comparing fluconazole and ketoconazole in combination with cephalexin for the treatment of dogs with malassezia dermatitis

This double-blinded noninferiority clinical trial evaluated the use of oral fluconazole for the treatment of Malassezia dermatitis in dogs by comparing it with use of an accepted therapeutic agent, ketoconazole. Dogs presenting with Malassezia dermatitis were treated with either fluconazole or ketoconazole in addition to cephalexin for concurrent bacterial dermatitis. Statistically significant improvements in cytologic yeast count, clinical signs associated with Malassezia dermatitis, and pruritus were seen with both antifungal treatments. There was no statistical difference between the treatments with regard to the magnitude of reduction in these parameters. These results suggest that fluconazole is at least as effective as ketoconazole for the treatment of dogs with Malassezia dermatitis.     

Effect of enrofloxacin on digoxin clearance and steady-state serum concentrations in dogs.

The effect of enrofloxacin on the oral clearance and steady-state concentrations of digoxin in serum was evaluated in dogs. Digoxin was administered orally to six healthy adult Beagle dogs following a multiple-dose regimen of 0.0625 mg every 12 h for 23 days. From days 14 to 23 enrofloxacin was administered orally at a dosage of 2.5 mg/kg every 12 h, with subjects receiving enrofloxacin 2 h prior to digoxin. Trough serum concentrations of digoxin were measured using an immunoassay technique. On days 13 and 22, dogs were catheterized for multiple blood sample collection during the 12 h digoxin dosing interval and serum samples were analyzed for digoxin concentrations. In general, steady-state digoxin concentrations in trough serum were not significantly different during enrofloxacin treatment than before enrofloxacin administration. Similarly, digoxin oral clearance was not significantly different between pre-enrofloxacin and digoxin + enrofloxacin periods. We conclude that enrofloxacin is unlikely to have a significant impact on digoxin disposition in dogs.     

Evaluation of serum and urine 1,5-anhydro-D-glucitol and myo-inositol concentrations in healthy dogs

1,5-anhydro-D-glucitol (1,5AG) is a pyranoid polyol compound found in human circulating blood. Myo-inositol (MI) is a stereoisomer of inositol and serves as a precursor of inositol phospholipids. 1,5AG and MI are filtered by the glomerulus and almost completely reabsorbed through the renal tubules. However, under hyperglycemic conditions, reabsorption through the renal tubules is competitively inhibited because the structures of 1,5AG and MI resemble that of glucose. In this study, we investigated the kinetics of serum and urine 1,5AG and MI levels in healthy dogs. We demonstrated that 1,5AG and MI exist in canine serum and urine by gas chromatography-mass spectrometry. Under continuous hyperglycemic conditions, the serum 1,5AG concentration in healthy dogs decreased while the serum MI concentration remained unchanged. Urinary excretion of 1,5AG and MI increased significantly after blood glucose concentrations reached 200 to 220 mg/dl. A significant negative correlation was observed between serum 1,5AG and glucose concentrations during hyperglycemia. However, no significant correlation was observed between serum MI and glucose concentrations. In this study, we demonstrated that serum and urine 1,5AG and MI levels were changed by blood glucose concentrations. The serum 1,5AG concentration was decreased by continuous hyperglycemia. However, the serum MI concentration does not reflect hyperglycemia.     

Evaluation of a continuous glucose monitoring system in diabetic dogs

The generation of a blood glucose curve is important for assessing the response to insulin therapy in diabetic dogs. Disadvantages of this technique include patient discomfort and the potential for missing transient hypo- or hyperglycaemic episodes. The aim of the current study was to evaluate a continuous glucose monitoring system (CGMS) for use in diabetic dogs. Interstitial fluid glucose concentrations were recorded in 10 diabetic dogs, every five minutes for up to 48 hours, using a subcutaneous sensor attached to the CGMS device. Blood glucose concentrations were measured simultaneously using a glucometer. The correlation between interstitial fluid and blood glucose values was 0.81 (P < 0.01). The largest discrepancies between the two sets of data were seen during the one- to three-hour period following feeding, suggesting that postprandial hyperglycaemia might not be reflected in the interstitial fluid. The authors conclude that the CGMS is a potentially valuable tool in the management of canine diabetic patients.     

Evaluation of the association between microalbuminuria and the urine albumin-creatinine ratio and systemic disease in dogs

OBJECTIVE: To evaluate semiquantitative and quantitative assays for microalbuminuria and determination of the urine albumin-creatinine (UAC) ratio in detection of systemic disease in dogs without overt proteinuria. DESIGN: Prospective study. ANIMALS: 408 dogs. PROCEDURES: Urine samples that had been obtained from dogs for which a complete medical record was available and in which results of a dipstick test for urine protein were negative were evaluated. Urine protein-creatinine ratios (cutoff values, 0.5 and 0.1), semiquantitative and quantitative microalbuminuria values (cutoff value, 1 mg/dL), and UAC ratios (cutoff values, 100 and 200 mg/g) were determined. Clinical diagnoses rendered within 3 months of enrollment in the study were recorded. Sensitivity and specificity were determined with disease status serving as the standard. Associations with clinical diagnosis, sex, age, BUN and serum creatinine concentrations, blood pressure, results of bacterial culture of urine, temperature, pyuria, hematuria, and bacteriuria were evaluated by use of logistic regression analysis. RESULTS: 48 dogs were healthy, and 360 had at least 1 disease. Significant associations were detected between age, presence of disease, presence of neoplastic disease, BUN and serum creatinine concentrations, and hematuria and results of 1 or both of the microalbuminuria assays. CONCLUSIONS AND CLINICAL RELEVANCE: Microalbuminuria was associated with underlying disease. The sensitivity and specificity of the semiquantitative microalbuminuria test for detection of systemic disease were superior to those of other tests. Microalbuminuria testing in conjunction with other screening procedures may increase diagnosis of subclinical disease, but a prospective study in which the predictive values of screening tests are evaluated, with and without microalbuminuria determination, is needed.     

Evaluation of five portable blood glucose meters for use in dogs

OBJECTIVE: To evaluate clinical and analytical accuracy of 5 portable blood glucose meters (PBGM) used to measure blood glucose concentrations in dogs and to determine potential sources of error. DESIGN: Prospective study. ANIMALS: 221 dogs. PROCEDURE: Venous blood samples were obtained, and results of the 5 PBGM were compared with results of a hexokinase reference method. Agreement among methods was determined by use of error grid analysis and statistical methods. RESULTS: Accuracy of the PBGM varied with glucose concentration of the sample. The largest differences between results of the PBGM and results of the reference method were obtained with samples with high glucose concentrations; 4 PBGM tended to underestimate and 1 PBGM tended to overestimate the true glucose concentration. Absolute differences between results of the PBGM and results of the reference method were small for samples with low glucose concentrations and samples with concentrations in the reference range. None of the PBGM yielded measurements that would result in clinically unacceptable errors. Within-run and between-day precision was good for all PBGM, and results were not affected by use of EDTA or heparin to anticoagulate blood. Readings of the PBGM were significantly higher for blood samples with low Hct than for samples with normal Hct. For 3 PBGM, samples < 3 microliters resulted in inaccurate measurements. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that currently available PBGM are sufficiently accurate for use in clinical practice to determine blood glucose concentrations in dogs.     

Evaluation of the reproducibility and accuracy of pH-determining devices used to measure urine pH in dogs

OBJECTIVE: To evaluate the reproducibility and accuracy of 4 portable pH meters, a reagent strip, and pH paper for measuring urine pH in dogs. DESIGN: Prospective masked randomized study. SAMPLE POPULATION: 201 free-catch urine samples from 114 hospitalized dogs. PROCEDURES: Urine samples were divided into 2-mL aliquots. Measurements of urine pH were obtained by use of a laboratory benchtop pH meter, 4 portable pH meters, a urine reagent strip, and pH paper. The pH of each aliquot was measured within 4 hours of collection by an evaluator unaware of the aliquot's origin.To assess reproducibility, the coefficient of variation for each pH measurement device was calculated. To determine which device was most accurate, the degree of agreement among the different devices was assessed in comparison with the benchtop pH meter, which was considered the reference method. RESULTS: 3 of the 4 portable pH meters had nearly perfect agreement with the reference method. The reagent strip and pH paper had moderate to poor agreement with the reference method. CONCLUSIONS AND CLINICAL RELEVANCE: Urine pH measurements should be made by use of a portable or benchtop pH meter when accurate measurements are crucial for diagnosis or treatment. Reagent strips and pH papers are useful in obtaining pH approximations but are not recommended when accurate measurements of urine pH are required.     

Evaluation of the effect of two dose rates of cyclosporine on the severity of perianal fistulae lesions and associated clinical signs in dogs

OBJECTIVE: To investigate the effect of cyclosporine (2 or 5 mg/kg every 24 hours) on perianal fistulae (PAF) lesions. STUDY DESIGN: Blinded randomized, prospective trial. ANIMALS: Dogs (n = 20) with perianal fistulae. METHODS: Dogs were randomly assigned to administration of either 2 mg/kg (n = 10) or 5 mg/kg (n=10) of cyclosporine orally every 24 hours for 8 weeks. Lesion surface area was measured, lesion severity was graded using a visual analog scale, and the presence and severity of clinical signs recorded every 2 weeks. RESULTS: Lesion variables were significantly reduced in both groups after 8 weeks and owners also reported a reduction in clinical sign severity. The 5 mg/kg dose rate significantly accelerated lesion resolution compared with 2 mg/kg. In the 2 mg/kg group, 20% of dogs had complete resolution of clinical signs and 10% had resolution of lesions. In the 5 mg/kg group, 40% of dogs had complete resolution of clinical signs and 60% had resolution of lesions. CONCLUSIONS: A dose rate of 5 mg/kg every 24 hours was more effective at reducing the surface area and severity of PAF lesions than 2 mg/kg every 24 hours but less effective at resolving PAF lesions than previous studies using dose rates > or =5 mg/kg every 12 hours. CLINICAL RELEVANCE: Cyclosporine at 5 mg/kg every 24 hours may be useful for the palliation of PAF lesions.