Assessment of the Potential for Veverimer Drug-Drug Interactions.

Veverimer is a polymer being developed as a potential treatment of metabolic acidosis in patients with chronic kidney disease. Veverimer selectively binds and removes hydrochloric acid from the gastrointestinal tract, resulting in an increase in serum bicarbonate. Veverimer is not systemically absorbed, so potential drug-drug interactions (DDIs) are limited to effects on the absorption of other oral drugs through binding to veverimer in the gastrointestinal tract or increases in gastric pH caused by veverimer binding to hydrochloric acid. In in vitro binding experiments using a panel of 16 test drugs, no positively charged, neutral, or zwitterionic drugs bound to veverimer. Three negatively charged drugs (furosemide, aspirin, ethacrynic acid) bound to veverimer; however, this binding was reduced or eliminated in the presence of normal physiologic concentrations (100-170 mM) of chloride. Veverimer increased gastric pH in vivo by 1.5-3 pH units. This pH elevation peaked within 1 hour and had returned to baseline after 1.5-3 hours. Omeprazole did not alter the effect of veverimer on gastric pH. The clinical relevance of in vitro binding and the transient increase in gastric pH was evaluated in human DDI studies using two drugs with the most binding to veverimer (furosemide, aspirin) and two additional drugs with pH-dependent solubility effecting absorption (dabigatran, warfarin). None of the four drugs showed clinically meaningful DDI with veverimer in human studies. Based on the physicochemical characteristics of veverimer and results from in vitro and human studies, veverimer is unlikely to have significant DDIs. SIGNIFICANCE STATEMENT: Patients with chronic kidney disease, who are usually on many drugs, are vulnerable to drug-drug interactions (DDIs). The potential for DDIs with veverimer was evaluated based on the known site of action and physicochemical structure of the polymer, which restricts the compound to the gastrointestinal tract. Based on the findings from in vitro and human studies, we conclude that veverimer is unlikely to have clinically significant DDIs.

Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial.

AIMS: To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial. METHODS AND RESULTS: Overall, 8399 patients with New York Heart Association class II-IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any diuretics (n = 6290 for loop diuretics, n = 496 for other diuretics); of those, recorded dosage data for loop diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post-randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on-treatment analysis. CONCLUSION: Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.

Outdoor temperature and survival benefit of empiric potassium in users of furosemide in US Medicaid enrollees: a cohort study.

OBJECTIVE: Heat is associated with elevated all-cause mortality, and furosemide-induced potassium depletion might be worsened by heat-induced sweating. Because empiric potassium is associated with a marked survival benefit in users of furosemide at a dose of ≥40 mg/day, we hypothesised that this empiric potassium's survival benefit would increase with higher temperature (≥24°C). DESIGN: Cohort study. SETTING: Outpatient setting, captured by Medicaid claims, supplemented with Medicare claims for dual enrollees, from 5 US states from 1999 to 2010, linked to meteorological data. POPULATION/PARTICIPANTS: Furosemide (≥40 mg/day) initiators among adults continuously enrolled in Medicaid for at least 1 year prior to cohort entry (defined as the day following the dispensing day of each individual's first observed furosemide prescription). EXPOSURE: Interaction between: (1) empiric potassium, dispensed the day of or the day following the dispensing of the initial furosemide prescription, and (2) daily average temperature and daily maximum temperature, examined separately. OUTCOME: All-cause mortality. RESULTS: In 1:1 propensity score matched cohorts (total n=211 878) that included 89 335 person-years and 9007 deaths, all-cause mortality rates per 1000 person-years were 96.0 (95% CI 93.2 to 98.9) and 105.8 (95% CI 102.8 to 108.9) for potassium users and non-users, respectively. The adjusted OR of all-cause mortality for potassium use declined (ie, its apparent protective effect increased) as temperature increased, from a daily average temperature of about 28°C and a daily maximum temperature of about 31°C. This relationship was not statistically significant with daily average temperature, but was statistically significant with daily maximum temperature (p values for the interaction of potassium with daily maximum temperature and daily maximum temperature squared were 0.031 and 0.028, respectively). CONCLUSIONS: The results suggest that empiric potassium's survival benefit among furosemide (≥40 mg/day) initiators may increase as daily maximum temperature increases. If this relationship is real, use of empiric potassium in Medicaid enrollees initiating furosemide might be particularly important on hot days.

Subcutaneous furosemide for the treatment of heart failure: a state-of-the art review.

The prevalence of heart failure (HF) is on the rise. By 2030, over eight million Americans (46% increase from current prevalence) will have heart failure. In the USA, approximately 30 billion dollars is spent annually on heart failure and this number will likely double in 2030. Thus, HF represents a significant economic burden. Acute decompensated heart failure (ADHF) is a clinical spectrum, which refers to increasing symptoms and signs of heart failure prompting an emergency room visit or hospitalization. In ADHF, inpatient administration of intravenous diuretic is the standard of care due to the variability in the absorption of oral diuretics. Within 30 days, 25-30% of these patients are readmitted with recurrent ADHF. Recent efforts have focused in reducing HF readmission, and thereby decreasing costs; hence, innovative outpatient treatment options have emerged. Subcutaneous furosemide use will potentially overcome the need to place intravenous lines, reduce associated expenses, and enable management of ADHF at home. This review presents data on the pharmacodynamics and pharmacokinetics of subcutaneous furosemide, scientific evidence on the use of this therapy in the palliative and hospice population, and its experimental use as an outpatient therapy and/or as a bridge from inpatient to home.

Edema of Advanced Cancer: Prevalence, Etiology, and Conservative Management-A Single Hospice Cross-Sectional Study.

CONTEXT: Edema of advanced cancer, seldom recognized in the literature, significantly impairs patient quality of life. OBJECTIVES: The purpose was to assess edema frequency, etiology, and impact on common symptoms and present its conservative management. METHODS: A prospective analysis of 784 patients admitted to a hospice was performed, of whom 119 were diagnosed with edema. For 18 patients with short life prognosis, an individually tailored physiotherapy (limb elevation, bandaging, manual lymphatic drainage, and Kinesio Taping) or subcutaneous needle drainage was administered. Forty-six patients with longer prognosis were treated by standardized limb bandaging (5-7 days) and re-evaluated, 28 of them with venous congestion resistant to enteral diuretics received supplementary furosemide infusion. RESULTS: Among those admitted with edema (96.6% with advanced cancer), 81.5% had bilateral and 10.9% generalized edema, 10.9% had lymphorrhea, 5.9% skin ulcerations, and in 27.7% edema was the main problem. The high mean comorbidity C3-index score (2.97) was observed. The main precipitating factors of the edema were chronic immobilization (79.8%) medications (58.8%), and congestive heart failure (28.6%). Before admission, 47.9% had received diuretics for edema and only 4.2% had physiotherapy. Among those re-evaluated (46 patients [84 limbs]), the mean reduction of limb volume (1.18L; 16.6%; P < 0.001) was accompanied by a decrease of edema symptoms/signs intensity and ESAS-Core by median 1 point (P < 0.002). CONCLUSION: Limb edema of advanced cancer occasionally treated by physical therapy concerns patients with numerous comorbidities and precipitating factors. It can be managed sufficiently with decongestive or supportive physiotherapy, depending on patients' life prognosis, symptom burden, edema stage, and progression.

Pharmacodynamic assessment of diuretic efficacy and braking in a furosemide continuous infusion model.

INTRODUCTION: Diuretic failure is a potential life-ending event but is unpredictable and poorly understood. The objectives of this study were to evaluate pharmacodynamic markers of furosemide-induced diuresis and to investigate mechanisms of diuretic braking in dogs receiving constant rate infusion (CRI) of furosemide. ANIMALS: Six healthy male dogs. METHODS: Raw data and stored samples from one arm of a previously published study were further analyzed to mechanistically investigate causes of diuretic braking in these dogs. Urine volume was recorded hourly during a 5-h furosemide CRI. Urine and blood samples were collected hourly to measure serum and urine electrolytes, urine aldosterone, and plasma and urine furosemide. Serum electrolyte fractional excretion was calculated. Urine sodium concentration was indexed to urine potassium (uNa:uK) and urine furosemide (uNa:uFur) concentrations, plasma furosemide concentration was indexed to urine furosemide concentration (pFur:uFur), and urine aldosterone was indexed to urine creatinine (UAldo:C). Temporal change and the relationship to urine volume were evaluated for these measured and calculated variables. RESULTS: Urine volume was significantly correlated with urine electrolyte amounts and with uNa:uK. The ratio of pFur:uFur decreased during the infusion, whereas furosemide excretion was unchanged. CONCLUSIONS: There was a strong relationship between urine volume and absolute urine electrolyte excretion. Urine volume was strongly correlated to uNa:uK, giving it potential as a spot indicator of urine production during diuresis. The decrease in uNa:uK over time during the infusion is consistent with mineralocorticoid modification of urinary electrolyte excretion, supporting renin-angiotensin-aldosterone activation as a cause of diuretic braking in this model.

Comparison of salt with low-dose furosemide and carperitide for treating acute decompensated heart failure: a single-center retrospective cohort study.

Hypertonic saline with furosemide has been proposed for a long time as an effective therapeutic option for the treatment of acute decompensated heart failure (ADHF). We previously reported the efficacy of continuous infusion of 1.7 % hypertonic saline plus low-dose furosemide in treatment for ADHF. Although this therapeutic strategy can be a useful option for effective decongestion in treatment for ADHF, there is no study that assesses the effect and safety of saline supplementation compared with standard therapy in Japan. The aim of this study was to investigate the efficacy, safety, and cost-effectiveness of 1.7 % hypertonic saline plus low-dose furosemide infusion compared with carperitide. We compared clinical outcomes, adverse events, and cost for patients receiving carperitide (carperitide group) with those for patients receiving 1.7 % hypertonic saline plus low-dose furosemide (salt group) during the initial hospitalization for ADHF. The cost analysis was performed on the basis of the previous report about cost-effectiveness of acute heart failure. A total of 175 ADHF patients received either carperitide (n = 111) or 1.7 % hypertonic saline plus low-dose furosemide infusion (n = 64) as initial treatment. There were no differences in length of hospital stay (27 ± 19 vs. 25 ± 16 day, p = 0.170) and infusion period (7.2 ± 6.1 vs. 8.4 ± 7.5 day, p = 0.474) between the two groups. The incidence of rehospitalization did not differ at 1 month (7.6 vs. 6.6 %, p = 1.000) and 1 year (36.8 vs. 37.7 %, p = 0.907) between the two groups. The Kaplan-Meier curves revealed no significant difference for 1 year all-cause mortality between the two groups (log-rank, p = 0.724). The single hospitalization cost was 95,314 yen lower and the yearly hospitalization cost 125,628 yen lower in the salt group compared with the carperitide group. Thus, intravenous 1.7 % hypertonic saline plus low-dose furosemide infusion is as effective as carperitide in terms of clinical outcome and is a cost-effective therapeutic strategy for the treatment of ADHF.

The diuresis clinic: a new paradigm for the treatment of mild decompensated heart failure.

BACKGROUND: Heart failure results in approximately 1 million hospital admissions annually in the United States and is the leading cause of 30-day readmissions. METHODS: This study explores the impact of a diuresis clinic on heart failure outcomes and cost. Data were collected prospectively on all consecutive patients who received intravenous diuretics and multidisciplinary care in the clinic from its establishment from October 2011 to December 2012, as well as a comparison cohort of patients with heart failure who were admitted to the hospital for <48 hours. The percentage of hospitalized days was calculated for both cohorts 180 days before and 180 days after each patient's index visit. RESULTS: In the diuresis clinic group, 106 patients (mean age, 68.2 ± 13 years; 48% were women) were treated over 328 visits (1-22 visits per person), with a mean intravenous furosemide dose of 100 mg, average urine output of 1460 ± 730 mL, and weight loss of 2.3 ± 1.8 kg. Days hospitalized decreased from 38.3 to 31.2 per 1000 patient-days after the index diuresis clinic visit (P < .01). In the comparison group, 143 patients (mean age, 69 ± 16 years; 54% were women) were admitted for <48 hours. Days hospitalized increased from 14.4 to 21.0 per 1000 patient-days after index admission (P < .01). On multivariate analysis, the diuresis clinic was associated with 3 fewer days in the hospital per 180 days per patient, with an estimated annual savings of $12,113 per patient. CONCLUSIONS: Compared with a brief hospital stay, treatment of mild decompensated heart failure in a diuresis clinic resulted in a substantial and cost-effective decline in the rate of subsequent hospitalization.

Diuretic 99mTc DTPA renography in assessment of renal function and drainage in infants with antenatally detected hydronephrosis.

BACKGROUND/AIM: The controversy over the postnatal management of infants with antenataly detected hydronephrosis (ANH) still exists. We presented the results of diuretic 99mTc diethylenetriamine pentaacetic acid (DTPA) renography in 30 infants with the antenatal diagnosis of unilateral renal pelvic dilatation. The aim of this study was to assess the renal function determined by the pattern of drainage and split renal function (SRF) on diuretic renography and to correlate these findings with anteroposterior pelvic diameter (APD) estimated by ultrasonography. METHODS: A total of 30 infants with 60 renal units (RU) (25 boys and 5 girls, median age 6.0 months, range 2-24) presented with unilateral hydronephrosis on ultrasound in the newborn period, underwent DTPA diuretic renal scintigraphy (F+15 protocol). The median APD evaluated on perinatal ultrasound was 15 mm (range 5-30). The postnatal associated clinical diagnosis were pelviureteric junction obstruction (PUJ), simple hydronephrosis, megaureter, vesicoureteral reflux (VUR) and posterior urethral valves in 11, 10, 6, 2 and 1 infant, respectively. Images and Tmax/2 after diuretic stimulation on the background subtracted renographic curves were used as the criteria for classifying the drainage as good, partial, and poor or no drainage. The SRF was calculated with the integral method. RESULTS: Good drainage was shown in 36/60, partial drainage in 13/60 and poor or no drainage in 11/60 RU. The SRF > 40% was observed in 55/60 RU, with no RU showing SRF lower than 23.5%. In infants with severe ANH the obstruction was not excluded in 94.1%. CONCLUSION: Diuretic renography in antenatally detected hydronephrosis should be a useful tool in postnatal follow up, especially in differentiating nonobstructive hydronephrosis from obstructive. It is also importanat to assess and monitor the SRF. Our results suggest that even in the presence of partial or no drainage, SRF may not be significantly impaired.

The challenge of providing palliative care to a rural population with cardiovascular disease.

PURPOSE OF REVIEW: There is a growing burden of end-stage cardiovascular disease in the aging Western world and a need to improve access to best evidence-based care, including patients located in rural areas. RECENT FINDINGS: Disparities are evident within rural settings for patients with cardiovascular disease. Useful guidelines exist to guide clinical services integration. Palliative care and cardiac services need to integrate their services defining the primary care lead with heart failure nurses coordinating. Earlier communication around disease implications, symptom burden and objectives of care feed into the integrated model for best and agreed outcomes to be achieved. Telehealth can assist a rural population when it is part of that integrated care model but more research on telemonitoring is required before conclusions can be drawn on the role of this expensive technology. Individual care plans can assist all involved. Subcutaneous furosemide may play a part in keeping a patient at home and with good palliative care the place of death can be the patient's home, if that is desired. SUMMARY: Rural patients with end-stage heart failure can be well supported at home as long as the model of care is united to support them. This includes heart failure nurse coordination based in the cardiac team, palliative care and general practice support.

[Effectiveness and adequacy of tolvaptan prescription in hospitalized patients]. / Efectividad y adecuación de la prescripción de tolvaptán en pacientes hospitalizados.

PURPOSE: To analyse the effectiveness of the use of Tolvaptan and the adequacy of Tolvaptan prescription at a tertiary level hospital. METHODS: Prospective observational study of Tolvaptan prescrip - tion from October of 2010 to December of 2011. RESULTS: 30 patients (60.0% males) were included, 50.0% of which were diagnosed with heart failure and 30.0% with SIADH. Tolvaptan allowed achieving sodium levels higher than 135 mEq/L in 53.3% of the patients with a mean baseline value of 125.3±7.3 mEq/L. The median treatment duration was 5.0 days (interquartile range=3-45). A significant increase of uric acid associated to Tolvaptan treatment was observed. The prescription was in agreement to what has been established in GFT in 63.3% of the cases. CONCLUSIONS: Tolvaptan increases sodium levels by 7.5 mEq/L, both in SIADH-associated hyponatremia and in heart failure, with an appropriate safety profile.

Objetivo: Analizar la efectividad del uso de tolvaptán y la adecuación de su prescripción en un hospital de tercer nivel. Método: Estudio observacional prospectivo de las prescripciones de tolvaptán desde octubre de 2010 hasta diciembre de 2011. Resultados: Se incluyeron 30 pacientes (60,0% varones), 50,0% diagnosticados de insuficiencia cardíaca y 30,0% de SIADH. Tolvaptán permitió alcanzar niveles de sodio superiores a 135 mEq/L en el 53,3% de los pacientes que partían con una media de 125,3±7,3 mEq/L. La mediana de días de tratamiento fue de 5,0 (rango intercuartílico = 3-45). Se observó un incremento significativo de los niveles de ácido úrico asociado al tratamiento con tolvaptán. La prescripción se adecuó a lo establecido en la GFT en el 63,3% de los casos. Conclusiones: Tolvaptán incrementa un 7,5 mEq/L los niveles de sodio tanto en hiponatremia secundaria al SIADH como en insuficiencia cardiaca.

Intravenous diuretic day-care treatment for patients with heart failure.

Fluid overload is a common manifestation of decompensated chronic heart failure. This paper reports on a pilot study that investigated whether intravenous (i.v.) furosemide administered on a cardiology day ward for three successive days was effective in improving the symptoms of patients with fluid overload and chronic heart failure. The results showed that 94.1% of patients reported an improvement in their breathlessness, with a marked weight loss in 88.2% of patients. There were no marked changes in blood pressure or renal function. Hospital admission was avoided in 94.1% of cases. The study concluded that i.v. diuretic treatment given in a hospital day-care setting is safe and effective, and that it reduces the need for hospital admissions. As a consequence, this reduces the associated financial costs of hospitalisation.

Clinical experience with low-dose continuous infusion of furosemide in acute heart failure: assessment of efficacy and safety.

INTRODUCTION: Clinical data are scarce for furosemide administered as a low-dose (<160 mg/24 hours) continuous intravenous infusion in acute heart failure (HF). Our purpose was to evaluate the efficacy and safety of low-dose continuous infusion of furosemide on diuretic response, renal function, and patient outcomes. METHODS: A retrospective study of patients with acute HF who received furosemide administered as a continuous infusion after initial therapy with intermittent boluses (usually 40-80 mg every 12 hours). End points included mean hourly urine output, incidence of acute renal injury, and outcome disparities of patients who developed acute renal injury. Comparison of patients with preserved and reduced left ventricular ejection fraction (LVEF) was also performed. RESULTS: The study included 150 patients (age 57 ± 13 years, male gender 61%, admission weight 87 ± 32 kg, LVEF 37 ± 15%, 28% preserved LVEF). Mean initial and maximum furosemide doses were 5.1 ± 1.1 mg/h and 6.2 ± 2.2 mg/h, respectively. Mean duration of therapy was 51.4 ± 67.5 hours. Continuous infusion of furosemide was associated with a significant increase in mean hourly urine output compared to baseline (150 ± 77 mL/h vs 116 ± 69 mL/h, P < .001). Acute renal injury developed in 19% of patients, with 70% of those occurring within the first 48 hours of therapy. Mean serum creatinine (baseline 1.55 ± 1.50 mg/dL vs at discharge 1.64 ± 1.61 mg/dL, P = .20) and estimated glomerular filtration rate (baseline 67 ± 39 mL/min vs at discharge 67 ± 43 mL/min, P = .89) did not significantly change over the course of the hospitalization. Development of acute renal injury was associated with poorer outcomes, higher furosemide dose, and longer duration of furosemide therapy. Diuretic response and safety were not different between patients with preserved or reduced LVEF. CONCLUSIONS: In patients with acute HF, furosemide administered as a low-dose continuous infusion was effective in achieving diuresis and was not associated with a detectable effect on renal function. This diuretic approach appeared to be similarly effective and safe in patients with preserved LVEF.

Leukocyte depletion during extracorporeal circulation allows better organ protection but does not change hospital outcomes.

BACKGROUND: Leukocyte filtration has been reported to reduce inflammatory damage during cardiopulmonary bypass. We evaluated the role of leukocyte filtration on hospital outcome and postoperative morbidity. METHODS: Eighty-two consecutive patients who underwent isolated coronary artery bypass grafting were randomly assigned (1:1) to receive leukocyte filters on both arterial and cardioplegia lines or standard arterial filters during cardiopulmonary bypass. Hospital outcome, postoperative markers of morbidity, and biochemical assays were compared. Data were collected preoperatively, intraoperatively, and postoperatively. Costs for patients receiving intraoperative leukofiltration were compared with control patients getting standard arterial filters. RESULTS: Hospital mortality and intensive care unit and hospital length of stay were similar. Although duration of ventilation and incidence of pneumonia were comparable, leukocyte-depleted patients showed a higher ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (p = 0.008) and lower need for postoperative noninvasive ventilation (p = 0.041). Control patients showed higher need for continuous furosemide infusion (p = 0.013) and for renal replacement therapy (p = 0.014), in association with higher serum creatinine (p = 0.038) and blood urea (p = 0.18) and lower glomerular filtration rate (p = 0.038). Leukocyte-depleted patients required lower doses of inotropic agents (p = 0.56), whereas troponin I leakage and incidence of postoperative atrial fibrillation were comparable. No differences were found in terms of postoperative cerebral dysfunction or neutrophil and platelet counts, as well as postoperative bleeding and need for transfusions. Finally, leukodepletion proved significantly cost-beneficial, with a 37% cost reduction. CONCLUSIONS: Although hospital outcomes were similar in terms of mortality and length of stay, the improvements in pulmonary, renal, and myocardial function, in association with the cost benefit, justify the use of leukocyte-depletion filters in the clinical practice.

Performing repeated noninvasive bedside measures of volume response to intravenous furosemide in acute pulmonary edema: a feasibility assessment.

Optimizing responses to intravenous furosemide (ivF) in acute pulmonary edema is limited by current insensitive noninvasive means of volume assessment. We conducted a pilot study to assess the feasibility of performing repeated measures of echocardiographic and bioimpedance analysis (BIA) parameters and test their response as noninvasive markers of volume response to ivF. We also aimed to identify the most potentially sensitive markers of this response. Patients receiving ivF for a clinical diagnosis of acute cardiogenic pulmonary edema were studied. Echocardiographic and BIA parameters were measured at 0, 0.5, 1, 2, and 3 h after ivF. Intraobserver variability for each parameter was determined. Thirty-one patients were enrolled who were receiving 40-100 mg of ivF. Transmitral (MV) early peak velocity following Valsalva maneuver and transtricuspid (TV) early peak velocity reduced significantly (P= 0.012 and 0.010, respectively), whereas MV deceleration time increased significantly (P= 0.006) in response to ivF. Short-axis inferior vena cava diameter (SIVC) in expiration and inspiration and SIVC corrected for body surface area in expiration and inspiration reduced significantly following ivF (P= 0.039, 0.020, 0.032, and 0.016, respectively). BIA estimates of extracellular water decreased significantly (P= 0.001), whereas impedance (Z) at currents of 5, 50, 100, and 200 kHz increased following ivF; the changes were significant with all but the last parameter (P < 0.0001, 0.006, 0.010, and 0.051, respectively). Maximal change from baseline for each parameter was greater than its respective intraobserver variability. Performing repeated measures of echocardiographic and BIA parameters is feasible in this unstable group of patients. The above panel of parameters could potentially be used to track volume response to ivF and, thus, to optimize treatment in acute pulmonary edema.

In vivo assessment of novel furosemide gastro-mucoadhesive delivery system based on a kind of anion ion-exchange fiber.

A novel gastro-mucoadhesive delivery system based on a kind of anion ion-exchange fiber has been developed. Furosemide (FM), which is site-specifically absorbed from the upper gastrointestinal (GI) tract, was used as model drug. A novel-modified dissolution system, which can also be called "flow through diffusion cell," was used to study the drug release from the drug fibers. The GI transit studies of the FM fiber complexes in rats and gamma imaging studies in volunteers were carried out to evaluate the gastro-mucoadhesive behavior of the fiber. The pharmacokinetic profile and parameters of the FM suspension and FM fiber in fasted and fed rats were measured, respectively. Studies on rats and volunteers provided evidence for the validity of the hypothesis that the drug fiber provided better gastro-mucoadhesive properties in vivo.

Assessment of diuretic effects and changes in plasma aldosterone concentration following oral administration of a single dose of furosemide or azosemide in healthy dogs.

OBJECTIVE: To determine the diuretic effects and changes in plasma aldosterone concentration (PAC) following oral administration of a single dose of furosemide or azosemide in healthy dogs. ANIMALS: 8 mixed-breed dogs. PROCEDURES: A single dose of furosemide (2 mg/kg), azosemide (1, 5, or 10 mg/kg), or placebo (bifidobacterium [1 mg/kg]) was administered orally (in random order at 7-day intervals) to each dog (5 treatments/dog). Urine and blood samples were collected before (2 hours after evacuation of the urinary bladder; baseline) and at intervals for 24 hours after drug treatment to assess urine volume and plasma and urine biochemical variables. RESULTS: Compared with baseline values, treatment with furosemide and azosemide (5 and 10 mg/kg) increased urine output for 1 to 2 hours and 2 to 4 hours, respectively. The 24-hour urine volume and urinary sodium excretion were significantly increased following furosemide and azosemide (5 and 10 mg/kg) treatments, compared with effects of placebo; these increases were dose dependent for azosemide, and increases were similar for furosemide and the 5 mg/kg dose of azosemide. Compared with other treatments, 24-hour urinary potassium excretion was significantly increased with azosemide at 10 mg/kg. Azosemide (5 and 10 mg/kg) significantly increased plasma total protein concentration and decreased plasma potassium concentration, compared with baseline values. Compared with the effect of placebo, PAC was significantly increased by furosemide and the 10 mg/kg dose of azosemide. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs, a moderate dose of azosemide caused sufficient diuretic action and increased PAC to a lesser extent than furosemide.

CT urography: the end of IVU?

A review of the literature on the diagnostic accuracy of multidetector computed tomography urography (MDCTU) and intravenous urography (IVU) reveals a lack of comparative studies. However, the available data indicate that MDCTU has a high diagnostic accuracy. MDCTU is also preferred by patients, as it does not require bowel preparation. Full acceptance of this technique by the urologist will depend on optimisation of the communication process with a careful selection of the images to be transmitted. MDCTU has a higher cost than IVU but allows some diagnostic algorithms to be simplified. The real concern potentially limiting the widespread use of MDCTU is its higher radiation dose when compared with IVU. Although low-dose protocols will soon be available, a substantial dose reduction can already be achieved by tailoring MDCTU to the clinical problem rather than using a standardised approach. Our analysis indicates that IVU will definitely lose any residual role it may still have. In our department, the last urographic procedure was performed in May 2006.

Technological development of 40mg furosemide tablets: equivalence and bioavaibility study in dogs

Furosemide (40mg) was administered to 20 street dogs, 10 males and 10 females, in two different pharmaceutical forms: (1) compressed furosemide 40mg formulated at the Federal University of Pernambuco (UFPE-tablet), and (2) a commercial formulation with equal bioequivalence produced by the Laboratory for Pharmaceutical Technology of Pernambuco State (LAFEPE), the LAFEPE-furosemide. The study aimed to evaluate the kinetics of dissolution of the UFPE-tablet in order to analyze the behavior of bioavailability of the best formulation for veterinary use. The plasmatic concentrations of furosemide for the determination of parameters of pharmacological kinetics were analyzed by high-performance liquid chromatographic method (HPLC). The in vitro study accomplished through physiochemical analyses demonstrated that the formulas of the furosemide tablets attained the pharmaceutical requirements in agreement with USP 23 and the Brazilian Pharmacopoeia. The evaluation accomplished in dogs with UFPE-tablets given in only dose demonstrated uniformity in blood levels indicating stability in maintenance of the pharmaceutical formulation and efficiency in absorption of the active compound. These values are not significantly different in relation to the 5 percent confidence limit. Regarding maximum concentration (Tmax) time and global bioavaibility assessed by AUC means, there were no considerable differences as well. UFPE-furosemide displayed 743.492µg/mL.h as AUC average value whereas LAFEPE-furosemide had an average of 537.284µg/mL.h.

Furosemida (40mg) foi administrada a 20 cães de rua (cães SRD), 10 machos e 10 fêmeas, em duas formas farmacêuicas distintas: (1) furosemida comprimido 40mg formulada na Universidade Federal de Pernambuco (UFPE-comprimido) e (2) uma formulação comercial bioequivalente produzida pelo Laboratório de Tecnologia Farmacêutica do Estado de Pernambuco (LAFEPE-furosemida). O estudo objetivou avaliar a cinética de dissolução do UFPE-comprimido para analisar o comportamento da liodisponibilidade dos comprimidos buscando a melhor formulação para uso veterinário. As concentrações plasmáticas de furosemida para determinação de parâmetros farmacocinéticos, foram analisadas por cromatografia líquida de alto desempenho (HPLC). O estudo in vitro realizado através de análises físico-químicas demonstrou que as fórmulas dos comprimidos de furosemida preencheram os requisitos farmacêuticos de acordo com USP 23 e a Farmacopéia Brasileira. Avaliações realizadas em cães da formulação UFPE-comprimidos administrados em dose única, demonstrou uma uniformidade nos níveis sangüíneos indicando estabilidade na manutenção da forma farmacêutica e eficiência na absorção do princípio ativo. Estes valores não são significativamente diferentes em relação ao limite de confiança de 5 por cento. Em relação a concentração de máximo (Tmax) e ao tempo de biodisponibilidade global avaliados por meios de AUC, não houve nenhuma diferença considerável. O comprimido UFPE-furosemide exibiu AUC de 743.492µg/mL.h e o LAFEPE-furosemide teve uma média de 537.284µg/mL.h.