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Pharmacogenetic and Pharmacokinetics of Naproxen and Associated Naproxen-esomeprazole

NCT03092193 · Status: COMPLETED · Phase: PHASE4 · Type: INTERVENTIONAL · Enrollment: 8

Last updated 2020-11-03

No results posted yet for this study

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.

Conditions

  • Poor Metabolizer Due to Cytochrome P450 CYP2C9 Variant
  • Poor Metabolizer Due to Cytochrome p450 CYP2C19 Variant

Interventions

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).

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).

Sponsors & Collaborators

  • Fundação de Amparo à Pesquisa do Estado de São Paulo

    collaborator OTHER_GOV

  • University of Sao Paulo

    lead OTHER

Principal Investigators

  • Adriana M Calvo, PhD · Bauru School of Dentistry/USP

Study Design

Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
60 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2017-03-01
Primary Completion
2017-10-01
Completion
2017-10-01

Countries

  • Brazil

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03092193 on ClinicalTrials.gov