Bioequivalence Study of Furosemide 40 mg Tablet in 24 Indonesian Healthy Volunteers

Bioequivalence Study of Furosemide in Indonesian Healthy Volunteers

The purpose of this research was to investigate whether Furosemide 40 mg tablet manufactured by PT. Kimia Farma Tbk was bioequivalent to its reference drug and Lasix® 40 mg Tablet manufactured by PT. Aventis Pharma, Indonesia.

Study Overview

• Status: Completed
• Conditions: Drug Use
• Intervention / Treatment: Drug: Furosemide 40 mg; Drug: Lasix® 40 mg Tablet

Detailed Description

Twenty four healty volunteers were given a single dose of Furosemide 40 mg Tablet or Lasix® 40 mg Tablet with 240 mL of water beneath fasting condition. Then the blood samples for Furosemide were drawn and analyzed using UPLC. All subjects sample plasma were analyzed for pharmacokinetic evaluation

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta Pusat, DKI Jakarta, Indonesia, 10520
      • PT Pharma Metric Labs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• have read the subject information and signed informed consent documents
• age 18 - 55 years
• body mass index between 18-25 kg/m2
• have a normal electrocardiogram
• blood pressure within normal range (systolic 90-120 mmHg and diastolic 60-80 mmHg)
• heart rate within normal range (60-100 bpm)
• with absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening
• acceptance to use protection (condom) during intercourse with their spouse throughout the study

Exclusion Criteria:

• those who are pregnant and/or nursing women
• those with a history of hypersensitivity to furosemide, or other diuretics or other ingredients in the drugs or a history of serious allergic reaction to any drug, a significant allergic disease, or allergic reaction
• those with a history or presence of medical condition which might significantly influence the pharmacokinetic of the study drug, e.g. chronic gastrointestinal disease, diarrhea, gastric surgery, renal insufficiency, hepatic dysfunction or cardiovascular disease.
• those with a history or presence of any coagulation disorder or clinically significant hematology abnormalities
• those who are using any medication (prescription or non-prescription drug, food supplement, herbal medicine), particularly the medication known to affect the pharmacokinetic of the study drug, within one week prior to the drug administration day
• those who have participated in any clinical study within 3 months prior to the study (< 90 days)
• those who have donated or lost 300 ml (or more) of blood within 3 months prior to the study
• those who smoke more than 10 cigarettes a day
• those who are positive to HIV, HBsAg, and HCV tests (to be kept confidential)
• those with a history of drug or alcohol abuse within 12 months prior to screening for this study
• those who are unlikely to comply with the protocol, e.g uncooperative attitude, inability to return for follow up visits, poor venous access

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Furosemide 40 mg tablet; volunteers received Furosemide 40 mg tablet with 240 mL of water	Drug: Furosemide 40 mg; Administered with 240 mL of water
Active Comparator: Lasix® 40 mg Tablet; volunteers received Lasix® 40 mg tablet with 240 mL of water	Drug: Lasix® 40 mg Tablet; Administered with 240 mL of water; Other Names: Furosemide 40 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Ratio of Maximum Concentration	The ratio between test drug and reference drug	before dosing (0 h) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours after drug administration
Geometric Mean Ratio of Area Under Curve	The ratio between test drug and reference drug	before dosing (0 h) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics Parameter	Maximum plasma concentration	before dosing (0 h) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours after drug administration
Pharmacokinetics Parameter	Area Under Curve from 0 to 24 hours	before dosing (0 h) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours after drug administration

Collaborators and Investigators

• Sponsor: PT. Kimia Farma (Persero) Tbk
• Collaborators: PT Pharma Metric Labs
• Investigators: Principal Investigator: Frans D Suyatna, PT Pharma Metric Labs; Study Director: I Gusti Putu Bagus Diana Virgo, PT Pharma Metric Labs

Publications and helpful links

General Publications

• Chow SC. Bioavailability and Bioequivalence in Drug Development. Wiley Interdiscip Rev Comput Stat. 2014;6(4):304-312. doi: 10.1002/wics.1310.
• Oh SW, Han SY. Loop Diuretics in Clinical Practice. Electrolyte Blood Press. 2015 Jun;13(1):17-21. doi: 10.5049/EBP.2015.13.1.17. Epub 2015 Jun 30.
• Najib N, Idkaidek N, Beshtawi M, Bader M, Admour I, Alam SM, Zaman Q, Dham R. Bioequivalence evaluation of two brands of furosemide 40 mg tablets (Salurin and Lasix) in healthy human volunteers. Biopharm Drug Dispos. 2003 Sep;24(6):245-9. doi: 10.1002/bdd.361.
• Shankar SS, Brater DC. Loop diuretics: from the Na-K-2Cl transporter to clinical use. Am J Physiol Renal Physiol. 2003 Jan;284(1):F11-21. doi: 10.1152/ajprenal.00119.2002.
• Brater DC. Diuretic therapy. N Engl J Med. 1998 Aug 6;339(6):387-95. doi: 10.1056/NEJM199808063390607. No abstract available.
• Sica DA. Diuretic use in renal disease. Nat Rev Nephrol. 2011 Dec 20;8(2):100-9. doi: 10.1038/nrneph.2011.175.
• Ponto LL, Schoenwald RD. Furosemide (frusemide). A pharmacokinetic/pharmacodynamic review (Part I). Clin Pharmacokinet. 1990 May;18(5):381-408. doi: 10.2165/00003088-199018050-00004.
• Midha KK, McKay G. Bioequivalence; its history, practice, and future. AAPS J. 2009 Dec;11(4):664-70. doi: 10.1208/s12248-009-9142-z. Epub 2009 Oct 6. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2019
• Primary Completion (Actual): January 17, 2020
• Study Completion (Actual): January 29, 2020

Study Registration Dates

• First Submitted: July 18, 2021
• First Submitted That Met QC Criteria: July 23, 2021
• First Posted (Actual): July 29, 2021

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: January 17, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: furosemide; bioequivalence; Indonesian healthy volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: 447/STD/PML/2019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No