Disposition and clinical use of bromide in cats

OBJECTIVE: To establish a dosing regimen for potassium bromide and evaluate use of bromide to treat spontaneous seizures in cats. DESIGN: Prospective and retrospective studies. ANIMALS: 7 healthy adult male cats and records of 17 cats with seizures. PROCEDURE: Seven healthy cats were administered potassium bromide (15 mg/kg [6.8 mg/lb], p.o., q 12 h) until steady-state concentrations were reached. Serum samples for pharmacokinetic analysis were obtained weekly until bromide concentrations were not detectable. Clinical data were obtained from records of 17 treated cats. RESULTS: In the prospective study, maximum serum bromide concentration was 1.1 +/- 0.2 mg/mL at 8 weeks. Mean disappearance half-life was 1.6 +/- 0.2 weeks. Steady state was achieved at a mean of 5.3 +/-1.1 weeks. No adverse effects were detected and bromide was well tolerated. In the retrospective study, administration of bromide (n = 4) or bromide and phenobarbital (3) was associated with eradication of seizures in 7 of 15 cats (serum bromide concentration range, 1.0 to 1.6 mg/mL); however, bromide administration was associated with adverse effects in 8 of 16 cats. Coughing developed in 6 of these cats, leading to euthanasia in 1 cat and discontinuation of bromide administration in 2 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Therapeutic concentrations of bromide are attained within 2 weeks in cats that receive 30 mg/kg/d (13.6 mg/lb/d) orally. Although somewhat effective in seizure control, the incidence of adverse effects may not warrant routine use of bromide for control of seizures in cats.     

Disposition of deracoxib in cats after oral administration

The pharmacokinetics of deracoxib in seven healthy cats were determined following a single oral (1 mg/kg) dose. Minimal variability among cats was found for all estimated pharmacokinetic variables. Terminal half-life (t(1/2)) was 7.9 hours. The mean maximum concentration (C(max)) was 0.28 microg/mL and was measured 3.64 hours after drug administration. Deracoxib was not detectable in the plasma after 60 hours. The compounded liquid formula was accepted readily, and no adverse effects were observed. Further studies are needed to determine the efficacy and safety of deracoxib after acute and chronic use in the cat.     

Disposition of cyclosporine after intravenous and multi-dose oral administration in cats

The aim of this study was to evaluate the disposition of cyclosporine after intravenous (i.v.) and oral administration and to evaluate single sampling times for therapeutic monitoring of cyclosporine drug concentrations in cats. Six adult male cats (clinically intact) were used. Two treatments consisting of a single i.v. cyclosporine (1 mg/kg) and multiple oral cyclosporine (3 mg/kg b.i.d p.o. for 2 weeks) doses. Whole blood cyclosporine concentrations were measured at fixed times by high performance liquid chromatography and pharmacokinetic values were calculated. Mean values for the i.v. data included AUC (7413 ng/mL.h), t1/2 distribution and elimination (0.705 and 9.7 h, respectively), Cmax (1513 ng/mL), and Vd(ss) (1.71 L/kg). Mean values for the oral data included AUC (6243 ng/mL.h), t1/2 of absorption and elimination (0.227 and 8.19 h, respectively), and Cmax (480.0 ng/mL). Bioavailability of orally administered cyclosporine was 29 and 25% on days 7 and 14 respectively. Whole blood comment cyclosporine concentration 2 h after administration (C2) better correlated with AUC on days 7 and 14 than trough plasma concentration (C12). The rate of oral cyclosporine absorption was less than expected and there was substantial individual variation. Therapeutic drug monitoring strategies for cyclosporine in cats should be re-evaluated.     

Post-prandial changes in canine plasma creatinine

Post-prandial changes of plasma creatinine and urea concentrations were found in healthy Beagle dogs fed a pelleted diet. Changes of plasma creatinine determined using an alkaline picrate method were confirmed by a more specific enzymatic method. The study also showed that alkaline picrate methods over-estimate plasma creatinine in dog plasma.     

High urinary corticoid/creatinine ratios in cats with hyperthyroidism

Measurement of the urinary corticoid : creatinine (C : C) ratio provides an assessment of cortisol secretion over a period of time. Therefore, this test is a very sensitive measure of adrenocortical function. The stress of the diagnostic procedure and nonadrenal disease may increase the urinary C : C ratio. In addition, diseases such as hyperthyroidism may influence the metabolic clearance of cortisol. To evaluate the effect of thyroid hormone excess, urinary C : C ratios were measured in 32 cats with hyperthyroidism and 45 healthy household cats. In 7 cats, urinary C : C ratios were measured both before and after treatment for hyperthyroidism. With data from the healthy cats, the reference range for the urinary C : C ratio was determined to be 8.0 to 42.0 X 10(-6). The urinary C : C ratios in the cats with hyperthyroidism (median, 37.5 x 10(-6); range, 5.9-169.5 x 10(-6)) were significantly (P = .001) higher than those in the healthy cats (median, 16 x 10(-6); range, 4.8-52.5 x 10(-6)). In 15 cats with hyperthyroidism, the urinary C : C ratios exceeded the upper limit of the reference range. Treatment for hyperthyroidism led to a marked decrease in urinary C : C ratios. The results of this study demonstrate that the urinary C : C ratio may be abnormally high in cats with hyperthyroidism, probably because of increased metabolic clearance of cortisol and activation of the pituitary-adrenocortical axis by disease. Although the clinical features of hyperthyroidism and hyperadrenocorticism in cats are different, hyperthyroidism should be ruled out when cats are suspected of hyperadrenocorticism on the basis of abnormally high urinary C : C ratios.     

Measurements of plasma endothelin immunoreactivity in healthy cats and cats with cardiomyopathy

Plasma concentrations of endothelin-1 (ET-1), the most potent endogenous pressor substance discovered to date, are abnormally high in humans with congestive heart failure (CHF), and they correlate with the degree of functional impairment. We sought first to validate a human sandwich ELISA kit that targets that portion of the amino acid sequence that is identical in cats. The assay demonstrated linearity (R2 = .9968) and parallelism (P = .5339), recovery of spiked human ET-1 in cat plasma averaged 98.7%, and intraassay precision had a coefficient of variation <10%. We subsequently determined ET-1 immunoreactivity in healthy cats and in cats with myocardial disease with and without CHF, systemic thromboembolism (STE), or both. Plasma ET-1 immunoreactivity was measured in 12 healthy cats and in 28 cats with primary myocardial disease, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive or unclassified cardiomyopathy (RCM and UCM), respectively. Plasma ET mean (95% CI) concentrations were 0.777 (0.6536-0.924) fmol/mL in the control cats, 1.427 (0.922-2.209) fmol/mL in 12 cats with cardiomyopathy (HCM = 11, RCM/UCM = 1) but without CHF or evidence of STE, and 2.360 (1.666-3.343) fmol/mL in 16 cats with cardiomyopathy (HCM = 8, RCM/UCM = 7, DCM = 1) and CHF (n = 15) or STE (n = 4). Plasma immunoreactivity of ET-1 was significantly higher in cats with myocardial disease without CHF/STE versus normal cats (P < .05) and in cats with myocardial disease with CHF/STE versus normal cats (P < .001).     

Comparison and reproducibility of plasma clearance of exogenous creatinine, exo-iohexol, endo-iohexol, and 51Cr-EDTA in young adult and aged healthy cats

BACKGROUND: Important characteristics determining the usefulness of a method for glomerular filtration rate (GFR) measurement are convenience, availability, and reproducibility. HYPOTHESIS: The use of different plasma clearance methods could lead to different results and differences in reproducibility. ANIMALS: Twelve healthy cats: 6 young adult cats (age 7-12 months), and 6 aged cats (age 9-12 years) were included in this study. METHODS: A cross-over design was used to compare the plasma clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT), endo-iohexol (PenICT), and chromium-51 ethylenediaminetetraacetic acid (51Cr-EDTA), and to investigate reproducibility of these methods. Cats of different ages were included to determine if differences in GFR in young adult versus aged cats would be detected with these methods. The PECCT, PexICT, and PenICT were performed in a combined manner. Plasma data were subjected to noncompartmental (creatinine, exo-iohexol, and endo-iohexol) or bicompartmental (51Cr-EDTA) analysis with a statistical moment approach. Area under the concentration-time curve was calculated using the trapezoidal rule with extrapolation to infinity. Statistical analyses were carried out using a random effects model. RESULTS: Globally, the 4 methods differed significantly (P < .0001) in GFR assessment. Clearance of exo-iohexol and chromium-51 ethylenediaminetetraacetic acid (51Cr -EDTA) showed the highest and lowest reproducibility, respectively. Only plasma clearance of creatinine differed significantly between young adult and aged cats. CONCLUSION AND CLINICAL IMPORTANCE: We found considerable differences in reproducibility of different GFR measurements. These findings should be taken into account not only in practice but also in future studies involving GFR measurement.     

Cortisol/creatinine ratio in urine (UCC) of healthy cats

In 31 healthy cats urine samples were taken to determine the cortisol/creatinine ratio (UCC) during hospitalisation and at home. The UCC of the samples, which had been taken in the clinic, was significantly higher (0-19 x 10(-6), Median 3 x 10(-6)) than the one of the samples taken at home (0-4 x 10(-6), Median 1 x 10(-6)). The parameter was neither influenced by the cat's age, sex or the fact that the cat stayed inside or outside, nor by the degree of visible agitation. Assay validation achieved good results regarding precision and accuracy of the measuring of cortisol and creatinine in the urine. The study shows that stress--caused by the visit to the veterinarian--can provoke a significant increase of UCC. Therefore, the parameter should be determined only from urine samples taken at home. Furthermore, it is important to notice that cortisol metabolites are measured in varying degree with the different assays. Therefore, it is inevitable that each laboratory generates its own reference values.     

Disposition of cyadox in domesticated cats following oral,intramuscular, and intravenous administration

Cyadox (CYX) is a synthetic antibacterial agent of quinoxaline with much lower toxic effects. A safety criterion of CYX for clinical use was established by studying the pharmacokinetics and metabolism of CYX after oral (PO), intramuscular (IM), and intravenous (IV) administration. CYX was administered in six domesticated cats (three males and three females) by PO (40 mg/kg.b.w.), IM (10 mg/kg.b.w.), and IV (10 mg/kg.b.w.) routes in a crossover pattern. Highly sensitive liquid chromatography with ultraviolet detection (HPLC-UV) method was developed for detection of CYX and its metabolites present in plasma, urine, and feces. The bioavailability of CYX after PO and IM routes was 4.37% and 84.4%. The area under curves (AUC), mean resident time (MRT), and clearance (CL) of CYX and its metabolites revealed that CYX quickly metabolized into its metabolites. The total recovery of CYX and its main metabolites was >60% after each route. PO delivery suggesting first pass effect in cats that might make this route suitable for intestinal infection and IM injection could be better choice for systemic infections. Less ability of glucuronidation did not show any impact on CYX metabolism. The findings of present study provide detailed information for evaluation of CYX.     

Use of urine albumin/creatinine ratio for estimation of proteinuria in cats and dogs

The clinical utility of the urine albumin/creatinine ratio (UAC) using a simplified analyzer for estimation of proteinuria was studied in cats and dogs. Measurement results for diluted feline and canine albumin standard solutions showed linearity. Although conversion formulas (y=1.28x+1.04 and y=1.67x+10.47 for cats and dogs, respectively) were necessary, urine albumin concentrations could be determined in both animals. In cats and dogs with proteinuria, the UAC changed parallel with the urine protein/ creatinine ratio (UPC), and the Log UAC and Log UPC were significantly correlated (r=0.803 (p<0.01) in cats, r=0.801 (p<0.01) in dogs). The UAC using an UAC analyzer could be used clinically as one of the basic in-hospital laboratory tests for estimation of proteinuria in cats and dogs.     

Relationship between plasma creatinine concentration and glomerular filtration rate in dogs

Glomerula filtration rate (GFR), plasma creatinine concentration (CR), and plasma urea nitrogen concentration (BUN) were measured in 129 adult dogs with reduced renal mass. A preliminary examination of the relationship between CR and GFR was conducted, and the inverse model (GFR vs. 1/CR) was chosen for further evaluation. The slope of the regression of GFR on 1/CR which was computed from actual data was not statistically different from a theoretical regression line generated from the clearance equation.
Evaluation of subsets of the population revealed no significant difference between male ( n = 69) and female (n = 60) dogs on the slope of the regression equations. Diets differing in protein concentration (16% protein, n = 35: 21% protein, n = 75: 32% protein, n = 19) did not cause a significant difference in the slope of the regression equations.
The regression equation and the confidence intervals generated in this study may be used to predict a probable range of GFR values from CR in individual dogs. Such values may be useful in adjusting drug dosages in dogs with renal disease. However, since the derived equation did not differ significantly from the theoretical inverse relationship between GFR and CR, it remains to be established whether the equation is advantageous.     

Evaluation of plasma C-terminal atrial natriuretic peptide in healthy cats and cats with heart disease

BACKGROUND: The clinical implications of evaluating C-terminal atrial natriuretic peptide (ANP) concentration in cats are still controversial. HYPOTHESIS: The objective of this study was to investigate the relationship between plasma C-terminal ANP concentration and left atrial pressure (LAP) in healthy cats with volume overload (study 1), and to compare plasma C-terminal ANP in normal cats and cats with cardiomyopathy (study 2). ANIMALS: Five healthy adult cats were used in study 1, and clinically healthy cats (n=8) and cats with cardiomyopathy (n=14) were used in study 2. METHODS: In study 1, cats were anesthetized and given acetated Ringer's solution (100 mL/kg/h for 60 minute) via the cephalic vein. Hemodynamic measurements and blood samples, collected from the jugular vein, were performed at 10-min intervals. In study 2, blood samples from normal cats and cats with cardiomyopathy were collected from the cephalic vein. The plasma C-terminal ANP concentration was determined by radioimmunoassay for human alpha-ANP. RESULTS: In study 1, volume overload significantly increased the C-terminal ANP concentration and LAP from baseline. The C-terminal ANP concentration was strongly correlated with the mean LAP. In study 2, age, E wave velocity, and the ratios of the left atrium to aorta were significantly higher in the cats with cardiomyopathy compared with the normal cats. The C-terminal ANP concentration was significantly higher in the cats with cardiomyopathy compared with the normal cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Our results suggest that the measurement of plasma C-terminal ANP in cats may provide additional information for the diagnosis of heart disease.     

Evaluation of coagulation markers in the plasma of healthy cats and cats with asymptomatic hypertrophic cardiomyopathy

BACKGROUND: Thrombosis and arterial thromboembolism are frequent complications of feline cardiomyopathy, especially when associated with left atrial enlargement. Markers of activated coagulation may be used to evaluate the coagulation status of cats with hypertrophic cardiomyopathy (HCM) in relation to left atrial size. OBJECTIVES: The objective of this study was to compare plasma concentrations of thrombin-antithrombin complex (TAT), D-dimer, and fibrin degradation products (FDP) between clinically healthy cats and cats with HCM. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and antithrombin activity were also compared and the association between left atrial (LA) size and coagulation results in cats with HCM was evaluated. METHODS: Blood samples from 19 clinically healthy cats and 20 cats with HCM were obtained. All cats with HCM were asymptomatic and had no signs of heart failure. LA diameter and LA to proximal aortic (Ao) diameter ratio (LA:Ao) were determined by echocardiography. RESULTS: Reference intervals for D-dimer and TAT concentrations in plasma of healthy cats were established as 0.09-0.32 microg/mL and 2.0-20.0 microg/L, respectively. TAT, D-dimer, and FDP concentrations were increased in 5, 3, and 2 cats with HCM, respectively. TAT and D-dimer concentrations, and PT and aPTT were not significantly different between groups. Antithrombin activity was significantly decreased in cats with HCM (P=.03) despite marked range overlap. LA and LA:Ao were not correlated with coagulation results. CONCLUSIONS: Laboratory evidence of hypercoagulability was found in 45% of cats with HCM. Left atrial size was not associated with laboratory evidence of hypercoagulability. Association between coagulation markers and risk of thrombosis has yet to be evaluated in cats with HCM.