Pharmacokinetic Interaction Between Ibuprofen and Acetaminophen, Tablets Administered Individually or in Combination

NCT ID: NCT05428306

Last Updated: 2022-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-23
• Study Completion Date: 2019-02-01

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, 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

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 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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A: Ibuprofen/ Acetaminophen in fixed dose

Pharmaceutical Form: Tablet Formula: Ibuprofen 200 mg/ Acetaminophen 500 mg Dosage: 400 mg / 1000 mg (2 tablets) Administration way: oral

Group Type: EXPERIMENTAL

A1: Ibuprofen/Acetaminophen Fixed dose combination (Laboratorios Silanes S.A. de C.V.)

Intervention Type: DRUG

Formula : 200 mg/ 500 mg Pharmaceutical Form: Tablet Dosage: 400 mg / 1000 mg (2 tablets) Administration way: oral

Group B: Ibuprofen

Pharmaceutical Form: tablets Dosage: 400 mg (1 tablet) Administration way: oral

Group Type: ACTIVE_COMPARATOR

A2: Ibuprofen (Motrin®, Pfizer S.A. de C.V.)

Intervention Type: DRUG

A2: Pharmaceutical Form: tablet Dosage: 400 mg (1 tablet) Administration way: oral

Group C: Acetaminophen

Pharmaceutical Form: Tablet Formula: Acetaminophen 500 mg Dosage: 1000 mg (2 tablets) Administration way: oral

Group Type: ACTIVE_COMPARATOR

A3: Acetaminophen (Tylenol caplets®, from Janssen-Cilag, S.A. de C.V.)

Intervention Type: DRUG

A3:Pharmaceutical Form: tablet Formula: Acetaminophen 500 mg Dosage: 1000 mg (2 tablets) Administration way: oral

Interventions

A1: Ibuprofen/Acetaminophen Fixed dose combination (Laboratorios Silanes S.A. de C.V.)

Formula : 200 mg/ 500 mg Pharmaceutical Form: Tablet Dosage: 400 mg / 1000 mg (2 tablets) Administration way: oral

Intervention Type: DRUG

A2: Ibuprofen (Motrin®, Pfizer S.A. de C.V.)

A2: Pharmaceutical Form: tablet Dosage: 400 mg (1 tablet) Administration way: oral

Intervention Type: DRUG

A3: Acetaminophen (Tylenol caplets®, from Janssen-Cilag, S.A. de C.V.)

A3:Pharmaceutical Form: tablet Formula: Acetaminophen 500 mg Dosage: 1000 mg (2 tablets) Administration way: oral

Intervention Type: DRUG

Other Intervention Names

IBU / ACETA; IBU; ACETA

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Laboratorios Silanes S.A. de C.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lourdes Garza Ocaña, M.D

Role: PRINCIPAL_INVESTIGATOR

Department of Pharmacology and Toxicology of the Faculty of Medicine of the U.A.N.L

Locations

Laboratorio Silanes, S.A. de C.V.

Mexico City, , Mexico

Countries

Mexico

References

Anderson BJ. Paracetamol (Acetaminophen): mechanisms of action. Paediatr Anaesth. 2008 Oct;18(10):915-21. doi: 10.1111/j.1460-9592.2008.02764.x.

Reference Type: BACKGROUND

PMID: 18811827 (View on PubMed)

Bramlage P, Goldis A. Bioequivalence study of three ibuprofen formulations after single dose administration in healthy volunteers. BMC Pharmacol. 2008 Oct 29;8:18. doi: 10.1186/1471-2210-8-18.

Reference Type: BACKGROUND

PMID: 18959779 (View on PubMed)

Tanner T, Aspley S, Munn A, Thomas T. The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol. BMC Clin Pharmacol. 2010 Jul 5;10:10. doi: 10.1186/1472-6904-10-10.

Reference Type: BACKGROUND

PMID: 20602760 (View on PubMed)

Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm. 1987 Dec;15(6):657-80. doi: 10.1007/BF01068419.

Reference Type: BACKGROUND

PMID: 3450848 (View on PubMed)

Other Identifiers

BD IP-Sil No.103-18

Identifier Type: -

Identifier Source: org_study_id