- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03092193
Pharmacogenetic and Pharmacokinetics of Naproxen and Associated Naproxen-esomeprazole
November 2, 2020 updated by: Adriana Maria Calvo, University of Sao Paulo
Clinical Pharmacokinetics of Cytochrome P450: Influence on the Pharmacokinetics of Naproxen (CYP2C8 and CYP2C9) and Associated Naproxen-esomeprazole (CYP2C19)
The family of cytochrome P450 (CYP) is the most important drug metabolizing enzymes which contributes to the metabolism of a large proportion of drugs in humans.
Some CYP450 enzymes reduce or alter the pharmacodynamic activity of many drugs and are involved in oxidative metabolism and elimination of many drugs commonly used by the population.
Polymorphisms in CYP2C8 and CYP2C9 are common in different populations around the world and genetic variations in these alleles can cause decreased enzyme activity to nonsteroidal anti-inflammatory drugs (NSAIDs) such as celecoxib, diclofenac, ibuprofen, indomethacin, lornoxicam, meloxicam, valdecoxib, piroxicam, tenoxicam and naproxen.
This compromise the bioavailability of the drug can alter the pharmacokinetics of these drugs and patients with mutations in these genes can exhibit increased plasma concentrations of values and areas under the curve (AUC), in addition to decreased clearance of drugs.
Associations between NSAIDs and gastric protectors or proton pump inhibitors (PPIs) have become common nowadays, especially in patients who make chronic use of these drugs.
Naproxen associated to esomeprazole, a proton pump inhibitor (PPI), was launched in the market recently and its application in acute pain is not yet elucidated.
Esomeprazole suffers strong influence of CYP2C19 (hepatic drug-metabolizing enzyme that degrades PPIs).
In patients with high enzyme activity of the CYP2C19, the drug can suffer high enzymatic degradation, and its diminished effect.
Moreover, in patients with low enzyme CYP2C19 activity, the effect of acid inhibition by PPIs can be very strong.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
The genotype presented by the patient in relation to CYP2C8, 2C9 and 2C19 could influence the absorption and metabolism of these NSAIDs with or without the gastric protectors, and may differ from anti-inflammatory action and side effects.
In this proposal, 20 volunteers will be genotyped and phenotyped for these haplotypes of cytochrome P450.
For analysis of the proposed genes, saliva will be collected as a source of genomic DNA.
For molecular analysis will be performed polymerase chain reaction (PCR) assays are used produced and validated by Applied Biosystems®.
For pharmacokinetics will be collected saliva samples at various times after ingestion of a tablet of naproxen (500 mg) or naproxen associated to esomeprazole (500 + 20 mg), using mass spectrometry for analysis of drug concentrations in the samples.
The results will be described with a 0.05 significance level.
Study Type
Interventional
Enrollment (Actual)
8
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
São Paulo
-
Bauru, São Paulo, Brazil, 17012-901
- Bauru School of Dentistry/USP
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Good general health
- Absence of infection and inflammation
- Absence of systemic diseases
Exclusion Criteria:
- patients with systemic diseases;
- patients with inflammation or infection;
- patients with a history of gastrointestinal bleeding or ulcerations;
- patients with cardiovascular, renal or hepatic diseases;
- patients who use antidepressant drugs, diuretics or anticoagulants;
- patients with a history of allergy to naproxen (500 mg);
- patients with a history of allergy to naproxen and ezomeprazole (500 mg and 20 mg);
- patients with a history of allergy to any other NSAID;
- pregnant and lactating women.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Naproxen
20 patients will receive naproxen (one tablet 500 mg) to collected saliva samples for pharmacokinetic and pharmacogenetic studies
|
20 phenotyped for CYP2C9 and CYP2C19 (by PCR) and for the pharmacokinetics of naproxen, saliva samples will be collected of these patients at different times after ingestion of a tablet of naproxen (500mg) (before, 0,25; 0,5; 0,75; 1; 1,5; 2; 3; 4; 5; 6; 8; 11; 24; 48; 72 e 96 hours after ingestion).
Other Names:
|
Experimental: Naproxen-esomeprazole
20 patients will receive after one month of first collection (with naproxen 500 mg), naproxen-esomeprazole (one tablet 500mg+20mg) to collected saliva samples for pharmacokinetic and pharmacogenetic studies
|
20 phenotyped for CYP2C9 and CYP2C19 (by PCR) and for the pharmacokinetics of naproxen-esomeprazole, saliva samples will be collected of these patients at different times after ingestion of a tablet of naproxen-esomeprazole (500mg+20mg) (after one month of the first collection) (before, 0,25; 0,5; 0,75; 1; 1,5; 2; 3; 4; 5; 6; 8; 11; 24; 48; 72 e 96 hours after ingestion).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Saliva concentration of naproxen
Time Frame: one week after the ingestion
|
20 phenotyped for CYP2C9 (by PCR) and for the pharmacokinetics of naproxen and naproxen-ezomeprazole saliva samples will be collected of these patients at different times after ingestion of a tablet of naproxen (500mg) (before, 0,25; 0,5; 0,75; 1; 1,5; 2; 3; 4; 5; 6; 8; 11; 24; 48; 72 e 96 hours after ingestion).
|
one week after the ingestion
|
Saliva concentration of naproxen-esomeprazole
Time Frame: one week after ingestion
|
20 phenotyped for CYP2C9 and CYP2C19 (by PCR) and for the pharmacokinetics of naproxen and naproxen-ezomeprazole saliva samples will be collected of these patients at different times after ingestion of a tablet of naproxen-esomeprazole (500mg+20mg) (before, 0,25; 0,5; 0,75; 1; 1,5; 2; 3; 4; 5; 6; 8; 11; 24; 48; 72 e 96 hours after ingestion).
|
one week after ingestion
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Chair: Adriana M Calvo, PhD, Bauru School of Dentistry/USP
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 1, 2017
Primary Completion (Actual)
October 1, 2017
Study Completion (Actual)
October 1, 2017
Study Registration Dates
First Submitted
March 15, 2017
First Submitted That Met QC Criteria
March 24, 2017
First Posted (Actual)
March 27, 2017
Study Record Updates
Last Update Posted (Actual)
November 3, 2020
Last Update Submitted That Met QC Criteria
November 2, 2020
Last Verified
November 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Gastrointestinal Agents
- Anti-Ulcer Agents
- Proton Pump Inhibitors
- Gout Suppressants
- Esomeprazole
- Naproxen
Other Study ID Numbers
- 49806115.0.0000.5417
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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