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Trial record 6 of 11 for:    tenoxicam

Pharmacogenetic and Pharmacokinetics of Naproxen and Associated Naproxen-esomeprazole

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ClinicalTrials.gov Identifier: NCT03092193
Recruitment Status : Unknown
Verified October 2017 by Adriana Maria Calvo, University of Sao Paulo.
Recruitment status was:  Recruiting
First Posted : March 27, 2017
Last Update Posted : October 25, 2017
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Adriana Maria Calvo, University of Sao Paulo

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Poor Metabolizer Due to Cytochrome P450 CYP2C9 Variant Poor Metabolizer Due to Cytochrome p450 CYP2C19 Variant Drug: Naproxen Drug: Naproxen-esomeprazole Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Clinical Pharmacokinetics of Cytochrome P450: Influence on the Pharmacokinetics of Naproxen (CYP2C8 and CYP2C9) and Associated Naproxen-esomeprazole (CYP2C19)
Actual Study Start Date : March 1, 2017
Estimated Primary Completion Date : July 1, 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Naproxen
20 patients will receive naproxen (one tablet 500 mg) to collected saliva samples for pharmacokinetic and pharmacogenetic studies
Drug: Naproxen
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 Name: CYP2C9

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
Drug: Naproxen-esomeprazole
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:
  • CYP2C9
  • CYP2C19




Primary Outcome Measures :
  1. 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).

  2. 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).



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03092193


Contacts
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Contact: Adriana M Calvo, PhD 551432358276 birinjela@yahoo.com.br

Locations
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Brazil
Bauru School of Dentistry/USP Recruiting
Bauru, São Paulo, Brazil, 17012-901
Contact: Adriana M Calvo, PhD    551432358276    birinjela@yahoo.com.br   
Sponsors and Collaborators
University of Sao Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
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Study Chair: Adriana M Calvo, PhD Bauru School of Dentistry/USP

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Responsible Party: Adriana Maria Calvo, Principal Investigator, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT03092193     History of Changes
Other Study ID Numbers: 49806115.0.0000.5417
First Posted: March 27, 2017    Key Record Dates
Last Update Posted: October 25, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Adriana Maria Calvo, University of Sao Paulo:
Naproxen
Association of naproxen-esomeprazole
High pressure liquid chromatography
Cytochrome P450
Additional relevant MeSH terms:
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Naproxen
Esomeprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gout Suppressants
Cyclooxygenase Inhibitors