Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs

Background Furosemide, a diuretic that acts on the loop of Henle, is commonly used to treat congestive heart failure in veterinary medicine. Some owners have difficulty in administering oral tablet medication to animal patients, which leads to noncompliance, especially during long-term administration. Oral disintegrating film (ODF) has the advantages of easy administration via a non-invasive route, rapid dissolution, and low suffocating risk. The objective of this study was to research the pharmacokinetic (PK) profiles and diuretic effect of furosemide after intravenous (IV), orally uncoated tablet (OUT), and newly developed ODF administration in healthy beagle dogs. In this study, a furosemide-loaded ODF (FS-ODF) formulation was developed and five beagle dogs were administered a single dose (2 mg/kg) of furosemide via each route using a cross-over design. Results The most suitable film-forming agent was sodium alginate; thus, this was used to develop an ODF for easy drug administration. No significant differences were detected in the PK profiles between OUT and FS-ODF. In the blood profiles, the concentration of total protein was significantly increased compared to the baseline (0 h), whereas no significant difference was detected in the concentration of creatinine and hematocrit compared to the baseline. FS-ODF resulted in a similar hourly urinary output to OUT during the initial 2 h after administration. The urine specific gravity was significantly decreased compared to the baseline in each group. The peak times of urine electrolyte (sodium and chloride) excretion per hour were 1 h (IV), 2 h (OUT), and 2 h (FS-ODF). Conclusions These results suggest that the PK/PD of furosemide after administration of newly developed FS-ODF are similar to those of OUT in healthy dogs. Therefore, the ODF formulation has the benefits of ease and convenience, which would be helpful to owners of companion animals, such as small dogs (< 10 kg), for the management of congestive heart failure.

Pharmacokinetics and Diuretic Effect of Furosemide after Single Intravenous, Oral Tablet, and Newly Developed Oral Disintegrating Film Administration in Healthy Beagle Dogs

Background: Furosemide, a diuretic that acts on the loop of Henle, is commonly used to treat congestive heart failure in veterinary medicine. Some owners have difficulty in administering oral tablet medication to animal patients, which leads to noncompliance, especially during long-term administration. The oral disintegrating film (ODF) has the advantages of easy administration via a non-invasive route, rapid dissolution, and low suffocating risk. The objective of this study was to research the pharmacokinetic and pharmacodynamics (PK/PD) profiles of furosemide after intravenous (IV), orally uncoated tablet (OUT), and newly developed ODF administration in healthy beagle dogs. In this study, a furosemide-loaded ODF (FS-ODF) formulation was developed and five beagle dogs were administered a single dose (2 mg/kg) of furosemide via each route using a cross-over design.Results: The most suitable film-forming agent was sodium alginate; thus, this was used to develop an ODF for easy drug administration. No significant differences were detected in the PK profiles between OUT and FS-ODF. The maximum plasma concentration of furosemide was higher and the elimination half-life and time at maximum concentration were slightly lower after FS-ODF administration than after OUT administration. In the blood profiles, the concentration of total protein was significantly increased compared to the baseline (0 h), whereas no significant difference was detected in the concentration of creatinine and hematocrit compared to the baseline. FS-ODF resulted in a similar hourly urinary output to OUT during the initial 2 h after administration. The urine specific gravity was significantly decreased compared to the baseline in each group. The peak times of urine electrolyte (sodium and chloride) excretion per hour were 1 h (IV), 2 h (OUT), and 2 h (FS-ODF). Conclusions: These results suggest that the PK/PD of furosemide after administration of newly developed FS-ODF are similar to those of OUT in healthy dogs. Therefore, the ODF formulation has the benefits of ease and convenience, which would be helpful to owners of companion animals, such as small dogs (<10 kg) or cats, for the management of congestive heart failure.

Congenital chloride diarrhoea

Congenital chloride diarrhoea is one of the rare causes of diarrhoea during infancy and it is infrequently reported throughout the world. It is an autosomal recessive condition which is more prevalent in Poland, Finland, Saudi Arabia and Kuwait while rarely reported in Pakistan. Our patient was 7.5-month-old baby boy who presented with diarrhoea since neonatal period. He had consanguineous parents. On examination, baby had distended abdomen, hypotonia and hyporeflexia. Investigations revealed hypochloremic hypokalemic metabolic alkalosis. Urinary electrolytes were normal. Stool electrolytes revealed increased stool chloride excretion that confirmed our diagnosis of congenital chloride diarrhoea. Patient was treated with intravenous fluids and electrolyte replacement, followed by oral potassium and sodium replacement. He was also started on butyrate, cholestyramine and proton-pump inhibitors. He started gaining weight during his hospital admission and is being followed up in clinic.

Pharmacological Npt2a Inhibition Causes Phosphaturia and Reduces Plasma Phosphate in Mice with Normal and Reduced Kidney Function

BackgroundThe kidneys play an important role in phosphate homeostasis. Patients with CKD develop hyperphosphatemia in the later stages of the disease. Currently, treatment options are limited to dietary phosphate restriction and oral phosphate binders. The sodium-phosphate cotransporter Npt2a, which mediates a large proportion of phosphate reabsorption in the kidney, might be a good therapeutic target for new medications for hyperphosphatemia.MethodsThe authors assessed the effects of the first orally bioavailable Npt2a inhibitor (Npt2a-I) PF-06869206 in normal mice and mice that had undergone subtotal nephrectomy (5/6 Nx), a mouse model of CKD. Dose-response relationships of sodium, chloride, potassium, phosphate, and calcium excretion were assessed in response to the Npt2a inhibitor in both groups of mice. Expression and localization of Npt2a/c and levels of plasma phosphate, calcium, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) were studied up to 24-hours after Npt2a-I treatment.ResultsIn normal mice, Npt2a inhibition caused a dose-dependent increase in urinary phosphate (ED50 approximately 21 mg/kg), calcium, sodium and chloride excretion. In contrast, urinary potassium excretion, flow rate and urinary pH were not affected dose dependently. Plasma phosphate and PTH significantly decreased after 3 hours, with both returning to near baseline levels after 24 hours. Similar effects were observed in the mouse model of CKD but were reduced in magnitude.ConclusionsNpt2a inhibition causes a dose-dependent increase in phosphate, sodium and chloride excretion associated with reductions in plasma phosphate and PTH levels in normal mice and in a CKD mouse model.

Blood and urinary variables in horses supplemented with electrolytes

This study was designed to evaluate changes on variables in blood, urine and water balance in horses in response to a single dose of electrolyte supplementation. The essay was conducted on a randomised 3×3 Latin Square design repeated over time, with three animals and three treatments: Treatment 1: control group (without supplementation); Treatment 2: supplementation with a medium dose of electrolytes composed of: 0.25 g of NaCl + 0.125 g of KCl + 0.05 g of CaCl + 0.025 g of MgCl per kg of BW; Treatment 3: supplementation with a high dose of electrolytes composed of: 0.625 g of NaCl + 0.3125 g of KCl + 0.125 g of CaCl + 0.0625 g of MgCl per kg of BW, equivalent to 2.5 times the medium dose of supplementation. The electrolytes were supplied through a nasogastric tube 4 h after the morning meal. The diet provided had a forage:concentrate ratio of 70:30, composed of coastcross hay and commercial concentrate, with an estimated consumption of 2% of body weigth (BW). Horses received 116 mg/kg of BW of commercial mineral salt mixed in the concentrate. Samples of blood, urine and digesta were collected over a 12 h period after supplementation for analysis of sodium, potassium, chloride, calcium and magnesium concentration. Water intake and urine output were also measured. Electrolytic supplementation enhanced (P<0.05) the water intake, water retention and urine output. Blood variables were not altered by electrolyte supplementation (P≯0.05). The supplementation also influenced the sodium and chloride excretion in urine (P<0.05). Urine physicochemical characteristics and the concentration of electrolytes excreted with time were significantly altered as a function of the electrolytes supplementation.