Pharmacogenetic and Pharmacokinetics of Naproxen and Associated Naproxen-esomeprazole

• Status: Completed
• Trial end date: 2017-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Sao Paulo
• Collaborator: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Treatments: Esomeprazole; Naproxen

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.