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 admi...

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Main Authors: Suk-Kyu Koh, Jong-Woo Jeong, Seo-In Choi, Rae Man Kim, Tae-Sung Koo, Kwan Hyung Cho, Kyoung-Won Seo
Format: Article
Language:English
Published: BMC 2021-09-01
Series:BMC Veterinary Research
Subjects:
Online Access:https://doi.org/10.1186/s12917-021-02998-4
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author Suk-Kyu Koh
Jong-Woo Jeong
Seo-In Choi
Rae Man Kim
Tae-Sung Koo
Kwan Hyung Cho
Kyoung-Won Seo
author_facet Suk-Kyu Koh
Jong-Woo Jeong
Seo-In Choi
Rae Man Kim
Tae-Sung Koo
Kwan Hyung Cho
Kyoung-Won Seo
author_sort Suk-Kyu Koh
collection DOAJ
description 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. 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.
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spelling doaj.art-4fc5366957894b449047b94430e893302022-12-21T22:37:15ZengBMCBMC Veterinary Research1746-61482021-09-0117111110.1186/s12917-021-02998-4Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogsSuk-Kyu Koh0Jong-Woo Jeong1Seo-In Choi2Rae Man Kim3Tae-Sung Koo4Kwan Hyung Cho5Kyoung-Won Seo6Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chungnam National UniversityGraduate School of New Drug Discovery and Development, Chungnam National UniversityDepartment of Veterinary Internal Medicine, College of Veterinary Medicine, Chungnam National UniversityCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje UniversityGraduate School of New Drug Discovery and Development, Chungnam National UniversityCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje UniversityDepartment of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National UniversityAbstract 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.https://doi.org/10.1186/s12917-021-02998-4CanineFurosemideLoop diureticOral filmTabletConventional administration
spellingShingle Suk-Kyu Koh
Jong-Woo Jeong
Seo-In Choi
Rae Man Kim
Tae-Sung Koo
Kwan Hyung Cho
Kyoung-Won Seo
Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs
BMC Veterinary Research
Canine
Furosemide
Loop diuretic
Oral film
Tablet
Conventional administration
title Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs
title_full Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs
title_fullStr Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs
title_full_unstemmed Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs
title_short Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs
title_sort pharmacokinetics and diuretic effect of furosemide after single intravenous oral tablet and newly developed oral disintegrating film administration in healthy beagle dogs
topic Canine
Furosemide
Loop diuretic
Oral film
Tablet
Conventional administration
url https://doi.org/10.1186/s12917-021-02998-4
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