Pharmacogenetic and Pharmacokinetics of Naproxen and Associated Naproxen-esomeprazole
Status:
Completed
Trial end date:
2017-10-01
Target enrollment:
Participant gender:
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
Details
Lead Sponsor:
University of Sao Paulo
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo