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

NCT05428306 | Completed Phase 1

• 1 other identifier: BD IP-Sil No.103-18
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy

Keywords

Pharmacokinetic; No interaction; Fixed-dose combination (FDC); Ibuprofen; Acetaminophen; Pain

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

Secondary Outcomes (6)

• 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

• 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

• 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

• 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

• Frequency of occurrence of adverse events

  1, 8 and 16 days

Study Arms (3)

Group A: Ibuprofen/ Acetaminophen in fixed dose

EXPERIMENTAL

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

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

Group B: Ibuprofen

ACTIVE COMPARATOR

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

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

Group C: Acetaminophen

ACTIVE COMPARATOR

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

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

Interventions

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

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

Also known as: IBU / ACETA

Group A: Ibuprofen/ Acetaminophen in fixed dose

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

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

Also known as: IBU

Group B: Ibuprofen

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

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

Also known as: ACETA

Group C: Acetaminophen

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laboratorios Silanes S.A. de C.V.: lead

Study Sites (1)

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

Mexico City, 11000, Mexico

Location

Related Publications (4)

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

  PMID: 18811827 BACKGROUND

• 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.

  PMID: 18959779 BACKGROUND

• 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.

  PMID: 20602760 BACKGROUND

• 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.

  PMID: 3450848 BACKGROUND

MeSH Terms

Conditions

Pain

Interventions

Acetaminophen; Ibuprofen

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids

Study Officials

• Lourdes Garza Ocaña, M.D

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2022
• First Posted: June 23, 2022
• Study Start: October 23, 2018
• Primary Completion: November 6, 2018
• Study Completion: February 1, 2019
• Last Updated: June 28, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)