Drug Use
Conditions
Keywords
bioequivalence, furosemide, Indonesian healthy volunteers
Brief summary
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.
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
Interventions
DRUGFurosemide 40 mg
Administered with 240 mL of water
DRUGLasix® 40 mg Tablet
Administered with 240 mL of water
Sponsors
PT Pharma Metric Labs
PT. Kimia Farma (Persero) Tbk
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
randomized, single blind, single dose, 2-period, cross-over design with one week washout period between each treatment in 24 healthy volunteers beneath fasting condition
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Ratio of Maximum 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 | The ratio between test drug and reference drug |
| Geometric Mean Ratio of Area Under Curve | 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 | The ratio between test drug and reference drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Parameter | 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 | Maximum plasma concentration |
Countries
Indonesia
Participant flow
Recruitment details
24 healthy volunteers were recruited from one research
Participants by arm
| Arm | Count |
|---|---|
| Total Number of Participants All volunteers received Furosemide 40 mg tablet with 240 mL of water new and marketed) | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Total Number of Participants | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 24 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 8 Participants | — |
| Sex: Female, Male Male | 16 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 5 / 24 | 5 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Geometric Mean Ratio of Area Under Curve
The ratio between test drug and reference drug
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Furosemide 40 mg Tablet | Geometric Mean Ratio of Area Under Curve | 101.79 percentage |
Primary
Geometric Mean Ratio of Maximum Concentration
The ratio between test drug and reference drug
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Furosemide 40 mg Tablet | Geometric Mean Ratio of Maximum Concentration | 104.51 percentage |
Secondary
Pharmacokinetics Parameter
Area Under Curve from 0 to 24 hours
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide 40 mg Tablet | Pharmacokinetics Parameter | 4938.79 ng*h/mL | Standard Deviation 1110.92 |
| Lasix® 40 mg Tablet | Pharmacokinetics Parameter | 4921.94 ng*h/mL | Standard Deviation 1279.14 |
Secondary
Pharmacokinetics Parameter
Maximum plasma concentration
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide 40 mg Tablet | Pharmacokinetics Parameter | 1893.09 ng/mL | Standard Deviation 479.62 |
| Lasix® 40 mg Tablet | Pharmacokinetics Parameter | 1907.32 ng/mL | Standard Deviation 707.72 |