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

Abstract

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.

Estimation of Furosemide Spectrophotometrically in Pharmaceutical preparations by Oxidative Coupling Reaction

“…Furosemide has potential interactions with these medications: Aspirin and other salicylates, other diuretics (e.g.ethacrynic acid, hydrochlorothiazide), Synergistic effects with other antihypertensives (e.g.doxazosin), and Sucralfate [6]. For the determination of furosemide, various analytical approaches have been used, spectrophotometry [7][8][9][10], HPLC [11][12][13][14], and other methods [15][16][17][18][19][20].…”