Healthy
Conditions
Keywords
Pharmacokinetic, Bioavailability, Fixed-dose combination (FDC), Etoricoxib, Tramadol, Pain
Brief summary
Study carried out in the Clinical and Analytical Unit of the Department of Pharmacology and Toxicology of the Faculty of Medicine of the Autonomous University of Nuevo León, with the objective of comparing the bioavailability (Cmax, AUC) of an oral formulation containing Etoricoxib 90 mg / Tramadol 50 mg in combination with that of two oral formulations, Etoricoxib 90 mg or Tramadol 50 mg, administered as a single dose, in healthy subjects under fasting conditions.
Detailed description
The study design was a crossover, 3 x 6 x 3, open-label, prospective and longitudinal, truncated, single-dose combination of Etoricoxib 90 mg / Tramadol 50 mg administered orally versus each component administered individually, with three treatments, three periods. , six sequences with an elimination period (washout) of 14 days and with a total of 42 healthy subjects, of both genders, under fasting conditions. Among the objectives were the characterization of the pharmacokinetic parameters, Cmax, AUC 0-72, Tmax, Ke and T1/2 of Etoricoxib and Tramadol after oral administration in a single dose, in combination: sachet with granules equivalent to Etoricoxib 90 mg/ Tramadol 50 mg manufactured by Laboratorios Silanes, S.A. of C.V. versus each component administered individually: Etoricoxib 90 mg tablet (Arcoxia®) manufactured by Schering Plough S.A de C.V. and Tramadol 50 mg capsule (Tradol®) made by Grunenthal GMBH (private company).
Interventions
DRUGA1: Etoricoxib / Tramadol Fixed dose combination
Sachet with granules (Laboratorios Silanes S.A. de C.V.). Formula : 90 mg/ 50 mg Pharmaceutical Form: Sachet with granules Dosage: 100 mL (90 mg/ 50mg) Administration way: oral
DRUGA2: Etoricoxib
Arcoxia®, Schering Plough S.A. de C.V. A2: Pharmaceutical Form: Tablet Formula: 90 mg Dosage: 1 tablet of 90 mg Administration way: oral
DRUGA3: Tramadol
Tradol®, from Grünenthal GMBH. Pharmaceutical Form: Capsule Formula: Each capsule contains 50 mg Dosage: 1 capsule of 50 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 (Federal Commission for the Protection against Sanitary Risks) 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 (Diagnostic and Statistical Manual of Mental Disorders) Criteria. * Research subjects who presents alterations in the vital signs recorded during the selection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Half time elimination (t1/2) | Baseline, 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12,0, 15.0, 24.0, 30.0, 36.0, 48.0 and 72.0 hours. | Evaluate the pharmacokinetics profile of the fixed dose Etoricoxib/Tramadol, employing the half time elimination (t1/2) by the quotient of Ln(2)Ke. |
| Time of the maximum measured concentration (Tmax). | Baseline, 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12,0, 15.0, 24.0, 30.0, 36.0, 48.0 and 72.0 hours. | Evaluate the fixed dose pharmacokinetics profile of Etoricoxib/Tramadol, employing time of the maximum measured concentration (tmax), Obtained graphically, from the plasma concentration profile with respect to time. |
| Elimination rate (Ke) | Baseline, 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12,0, 15.0, 24.0, 30.0, 36.0, 48.0 and 72.0 hours. | Evaluate the fixed dose pharmacokinetics profile of Etoricoxib/Tramadol, 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) |
| Maximum observed concentration following the treatment (Cmax) | Baseline, 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12,0, 15.0, 24.0, 30.0, 36.0, 48.0 and 72.0 hours. | Evaluate the pharmacokinetics profile of the fixed dose Etoricoxib/Tramadol, 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, 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12,0, 15.0, 24.0, 30.0, 36.0, 48.0 and 72.0 hours. | Evaluate the fixed dose pharmacokinetics profile of Etoricoxib/Tramadol, employing the area under the curve from time zero to the last measurable concentration (AUC 0-t) using the linear trapezoidal method. |
| The area under the curve from time zero to infinity calculated (AUC 0-inf), | Baseline, 0.25, 0.50, 0.75, 1.00, 1.50, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12,0, 15.0, 24.0, 30.0, 36.0, 48.0 and 72.0 hours. | Evaluate the fixed dose pharmacokinetics profile of Etoricoxib/Tramadol, employing the area under the curve from time zero to infinity calculated (AUC 0-inf). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 1, 15 and 29 days | Any adverse event were classified by severity, treatment and its relationship with the study drug was evaluated. |
| Determine the frequency of occurrence of adverse events | 1, 15 and 29 days | The percentage of frequency of appearance of each adverse event was evaluated. |
Countries
Mexico
Outcome results
None listed