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, with the aim of comparing the bioavailability (Cmax, AUC) of an oral formulation containing ibuprofen 400 mg/ Acetaminophen 1000 mg in combination with the two oral formulations ibuprofen 400 mg or Acetaminophen 1000 mg administered as a single dose, in healthy subjects under fasting conditions
The study design was crossover, 3 x 6 x 3, open, prospective and longitudinal, at a single dose of the combination of Ibuprofen 200mg/ Acetaminophen 500mg (2 tablets), administered orally versus each component administered individually Ibuprofen 400mg (1 tablet) or Acetaminophen 500 mg (2 tablets), with three treatments, three periods, six sequences with an elimination period (washout) of 1 week and with a number of 42 healthy subjects, of both genders, under fasting conditions. In order to compare the pharmacokinetic profile (Cmax and AUC 0-t) of the combination Ibuporfen/Acetaminophen 200 mg / 500 mg, single dose versus each component administered individually, to establish the non-interaction of the drugs in combination. Like, Characterize the pharmacokinetic parameters, Cmax and AUC 0-t, AUC 0-, Tmax, Ke and T1/2, of Ibuprofen and Acetaminophen after oral administration in a single dose. The frequency and type of adverse events with the two formulations were established.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Formula : 200 mg/ 500 mg Pharmaceutical Form: Tablet Dosage: 400 mg / 1000 mg (2 tablets) Administration way: oral
A2: Pharmaceutical Form: tablet Dosage: 400 mg (1 tablet) Administration way: oral
A3:Pharmaceutical Form: tablet Formula: Acetaminophen 500 mg Dosage: 1000 mg (2 tablets) Administration way: oral
Laboratorio Silanes, S.A. de C.V.
Mexico City, Mexico
Maximum observed concentration following the treatment (Cmax),
Evaluate the pharmacokinetics profile of the fixed dose Ibuprofen/Acetaminophen, employing the maximum observed concentration following the treatment (Cmax), obtained graphically, from the plasma concentration profile with respect to time.
Time frame: 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
The area under the curve from time zero to the last measurable concentration (AUC 0-t)
Evaluate the fixed dose pharmacokinetics profile of Ibuprofen/Acetaminophen, employing the area under the curve from time zero to the last measurable concentration (AUC 0-t) using the linear trapezoidal method.
Time frame: 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
The area under the curve from time zero to infinity calculated (AUC 0-inf)
Evaluate the fixed dose pharmacokinetics profile of Ibuprofen/Acetaminophen, employing the area under the curve from time zero to infinity calculated (AUC 0-inf).
Time frame: 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
Time of the maximum measured concentration (Tmax)
Evaluate the fixed dose pharmacokinetics profile of Ibuprofen/Acetaminophen employing time of the maximum measured concentration Tmax), Obtained graphically, from the plasma concentration profile with respect to time.
Time frame: 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
Elimination rate (Ke)
Evaluate the fixed dose pharmacokinetics profile of Ibuprofen/Acetaminophen, 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)
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Time frame: 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
Half time elimination (t1/2)
Evaluate the pharmacokinetics profile of the fixed dose Ibuprofen/Acetaminophen, employing the half time elimination (t1/2) by the quotient of Ln(2)Ke.
Time frame: 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
Frequency of occurrence of adverse events
The percentage of frequency of appearance of each adverse event was evaluated.
Time frame: 1, 8 and 16 days
Adverse Events
Any adverse event were classified by severity, treatment and its relationship with the study drug was evaluated.
Time frame: 1, 8 and 16 days