Healthy
Conditions
Keywords
Pharmacokinetic, Bioavailability, Fixed-dose combination (FDC), Ibuprofen, Acetaminophen, Oral suspension, Pain
Brief summary
This study was carried out in the Clinical and Analytical Unit of the Pharmacology and Toxicology Department of the Faculty of Medicine of the Autonomous University of Nuevo León, in order to compare the bioavailability (Cmax, AUC) of an oral formulation containing Ibuprofen 100 mg/Acetaminophen 125 mg in combination with the two oral formulations Ibuprofen 100 mg or Acetaminophen 125 mg administered as a single dose, in healthy subjects under fasting conditions.
Detailed description
The study design was crossover, 3 x 6 x 3, open, prospective and longitudinal, at a single dose, of the combination of Ibuprofen 100 mg/Acetaminophen 125 mg/5 mL suspension, administered orally versus each component administered individually Ibuprofen 100 mg/5 mL or Acetaminophen 125 mg/3.9 mL, with an elimitation period (washout) of 1 week. In order to compare the pharmacokinetic profile (Cmax and AUC0-t) of the Ibuprofen/Acetaminophen combination 100 mg/125 mg/5 mL, versus each component administered individually, in 42 healthy subjects, of both genders, under fasting conditions, to establish the interaction of drugs in combination. As well as, to characterize the pharmacokinetic parameters, Cmax and AUC0-t, AUC0-∞, Tmax, Ke, and T1/2 and to establish the frequency and type of adverse events with the two formulations.
Interventions
DRUGA1: Ibuprofen/Acetaminophen Fixed dose combination oral suspension (Laboratorios Silanes S.A. de C.V.)
Formula : 100 mg/ 125 mg /5mL Pharmaceutical Form: Oral suspension Dosage: 5mL (100 mg/125mg) Administration way: oral
DRUGA2: Ibuprofen (Advil®, Pfizer S.A. de C.V.)
Pharmaceutical Form: oral suspension Formula: 2 g/100 mL Dosage: 5 mL(100 mg of Ibuprofen) Administration way: oral
DRUGA3: Acetaminophen (Tylenol®, from Janssen-Cilag, S.A. de C.V.)
Pharmaceutical Form: oral suspension Formula: 3.2 g/100 mL Dosage: 3.9 mL (125 mg) Administration way: oral
Sponsors
Laboratorios Silanes S.A. de C.V.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* The subjects must have been accepted by the COFEPRIS research subjects registration database. * Subjects without a subordinate relationship with the researchers. * Subjects who have given informed consent in writing. * Subjects of both genders, aged between 18 and 55 years, Mexicans. - -Subjects with no background of hypersensitivity or allergies to the drug under study or related drugs. * Body mass index between 18 and 27 kg/m2. * Healthy subjects, according to the results of the complete clinical history, electrocardiogram and the integration of the results of the clinical analyses, carried out in certified clinical laboratories, without alterations that require a medical intervention as a consequence. * Subjects with negative results for immunological tests (Anti-HIV, Anti-hepatitis B and C, VDRL). * Subjects with negative results in drug abuse screening tests: tetrahydrocannabinoids, cocaine and amphetamines. * Negative (qualitative) pregnancy test for women of childbearing potential without Bilateral tubal obstruction or hysterectomy. * In the case of women of childbearing age, they must have a birth control method, including barrier methods, non-hormonal intrauterine device, or bilateral tubal obstruction.
Exclusion criteria
* Subjects with recent history or physical examination evidence of gastrointestinal, renal, hepatic, endocrine, respiratory, cardiovascular, dermatological, or hematological disease that could affect the pharmacokinetic study of the product in research. * Subjects who have been exposed to drugs known as liver enzyme inducers or inhibitors or who have taken drugs potentially toxic within 30 days before the start of the study. * Subjects who have received any medication during the 7 days before the start of the study. * Subjects who have been hospitalized for any problem during the three months before the start of the study. * Subjects who have been rejected by the registry database of research subjects of COFEPRIS, for having participated in a clinical study within the three months prior to the start of the study. * Subjects who have received investigational drugs within the previous 60 days th the start of the study. * Subjects allergic to the study drug or related drugs. * Subjects who have ingested alcohol or drinks containing xanthines (coffee, tea, cocoa, chocolate, cola) or who have eaten charcoal-grilled food or grapefruit juice , at least 10 hours before the start of the study or who have smoked tobacco 24 hours before to the start of the internment period. * Subjects who have donated or lost 450 mL or more of blood within the previous 60 days of the beginning of the study. - Subjects with a history of drug and/or alcohol abuse according to the DSM-IV-TR Criteria. * Research subjects who presents alterations in the vital signs recorded during the selection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed concentration following the treatment (Cmax) | Baseline, 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12,0 and 14.0 hours. | Evaluate the pharmacokinetics profile of the fixed dose Ibuprofen/Acetaminophen oral suspension, employing the maximum observed concentration following the treatment (Cmax), obtained graphically, from the plasma concentration profile with respect to time. |
| The area under the curve from time zero to the last measurable concentration (AUC 0-t) | Baseline, 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12,0 and 14.0 hours. | Evaluate the fixed dose pharmacokinetics profile of Ibuprofen/Acetaminophen oral suspension, employing the area under the curve from time zero to the last measurable concentration (AUC 0-t) using the linear trapezoidal method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Elimination rate (Ke) | Baseline, 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12,0 and 14.0 hours. | Evaluate the fixed dose pharmacokinetics profile of ibuprofen/Acetaminophen oral suspension, employing the elimination rate (Ke), estimated from the terminal linear portion of the plasma concentration profile with respect to time (on a semi-log scale) |
| Half time elimination (T1/2) | Baseline, 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12,0 and 14.0 hours. | Evaluate the pharmacokinetics profile of the fixed dose ibuprofen/Acetaminophen oral suspension, employing the half time elimination (T1/2) by the quotient of Ln(2)Ke. |
| The area under the curve from time zero to infinity calculated (AUC 0-inf) | Baseline, 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12,0 and 14.0 hours. | Evaluate the fixed dose pharmacokinetics profile of ibuprofen/Acetaminophen oral suspension, employing the area under the curve from time zero to infinity calculated (AUC 0-inf) |
| Adverse events | 1, 8 and 16 days | Any adverse event was classified by severity, treatment and its relationship with the study drug evaluated. |
| Frequency of occurrence of adverse events | 1, 8 and 16 days | The percentage of frequency of appearance of each adverse event was evaluated. |
| Time of the maximum measured concentration (Tmax) | Baseline, 0.16, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12,0 and 14.0 hours. | Evaluate the fixed dose pharmacokinetics profile of ibuprofen/Acetaminophen oral suspension, employing time of the maximum measured concentration Tmax), obtained graphically, from the plasma concentration profile with respect to time. |
Countries
Mexico
Outcome results
None listed