Ignite Creation Date:
2024-05-06 @ 9:53 AM
Last Modification Date:
2024-10-26 @ 12:20 PM
Study NCT ID:
NCT03092193
Status:
COMPLETED
Last Update Posted:
2020-11-03
First Post:
2017-03-15
Brief Title:
Pharmacogenetic and Pharmacokinetics of Naproxen and Associated Naproxen-esomeprazole
Sponsor:
University of Sao Paulo
Organization:
University of Sao Paulo
Study Overview
Official Title:
Clinical Pharmacokinetics of Cytochrome P450 Influence on the Pharmacokinetics of Naproxen CYP2C8 and CYP2C9 and Associated Naproxen-esomeprazole CYP2C19
Status:
COMPLETED
Status Verified Date:
2020-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 005 significance level
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None