Naproxen - How It Works
Clinical pharmacology details from the US FDA-approved label: how Naproxen works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Naproxen and esomeprazole magnesium delayed-release tablets consist of an immediate-release esomeprazole magnesium layer and an enteric-coated naproxen core. As a result, esomeprazole is released first in the stomach, prior to the dissolution of naproxen in the small intestine. The enteric coating prevents naproxen release at pH levels below 5.5. The mechanism of action of the naproxen anion, like that of other NSAIDs, is not completely understood but inhibition of cyclooxygenase (COX-1 and COX-2). Naproxen and esomeprazole magnesium delayed-release tablets have analgesic, anti-inflammatory, and antipyretic properties contributed by the naproxen component. Naproxen is a potent inhibitor of prostaglandin synthesis in vitro . Naproxen concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. B
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Naproxen and esomeprazole magnesium delayed-release tablets consist of an immediate-release esomeprazole magnesium layer and an enteric-coated naproxen core.
As a result, esomeprazole is released first in the stomach, prior to the dissolution of naproxen in the small intestine.
The enteric coating prevents naproxen release at pH levels below 5.5.
The mechanism of action of the naproxen anion, like that of other NSAIDs, is not completely understood but inhibition of cyclooxygenase (COX-1 and COX-2).
Naproxen and esomeprazole magnesium delayed-release tablets have analgesic, anti-inflammatory, and antipyretic properties contributed by the naproxen component.
Naproxen is a potent inhibitor of prostaglandin synthesis in vitro .
Naproxen concentrations reached during therapy have produced in vivo effects.
Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models.
Prostaglandins are mediators of inflammation.
Because naproxen is an inhibitor of prostaglandin synthesis, its mode of action may be due to an increase of prostaglandins in peripheral tissues.
Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H + /K + -ATPase in the gastric parietal cell.
Esomeprazole is protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide.
By acting specifically on the proton pump, esomeprazole blocks the final step in acid production, thus reducing gastric acidity.
This effect is dose-related up to a daily dose of 20 mg to 40 mg and leads to inhibition of gastric acid secretion.
12.2 Pharmacodynamics Interaction with Aspirin In a healthy volunteer study, 10 days of concomitant administration of naproxen 220 mg once-daily with low-dose immediate-release aspirin (81 mg) showed an interaction with the antiplatelet activity of aspirin as measured by % serum thromboxane B 2 inhibition at 24 hours following the day 10 dose [98.7% (aspirin alone) vs 93.1% (naproxen and aspirin)].
The interaction was observed even following discontinuation of naproxen on day 11 (while aspirin dose was continued) but normalized by day 13.
In the same study, the interaction was greater when naproxen was administered 30 minutes prior to aspirin [98.7% vs 87.7%] and minimal when aspirin was administered 30 minutes prior to naproxen [98.7% vs 95.4%].
Following administration of naproxen 220 mg twice-daily with low-dose immediate-release aspirin (first naproxen dose given 30 minutes prior to aspirin), the interaction was minimal at 24 h following day 10 dose [98.7% vs 95.7%].
However, the interaction was more prominent after discontinuation of naproxen (washout) on day 11 [98.7% vs 84.3%] and did not normalize completely by day 13 [98.5% vs 90.7%] [see Drug Interactions ].
Antisecretory Activity The effect of naproxen and esomeprazole magnesium delayed-release tablets on intragastric pH was determined in 25 healthy volunteers in one study.
Pharmacokinetics
12.3 Pharmacokinetics Absorption Naproxen At steady state following administration of naproxen and esomeprazole magnesium delayed-release tablets twice daily, peak plasma concentrations of naproxen are reached on average 3 hours following both the morning and the evening dose. Bioequivalence between naproxen and esomeprazole magnesium delayed-release tablets and enteric-coated naproxen, based on both area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C max ) of naproxen, has been demonstrated for both the 375 mg and 500 mg doses. Naproxen is absorbed from the gastrointestinal tract with an in vivo bioavailability of 95%. Steady-state levels of naproxen are reached in 4 to 5 days. Esomeprazole Following administration of naproxen and esomeprazole magnesium delayed-release tablets twice daily, esomeprazole is rapidly absorbed with peak plasma concentration reached within on average, 0.43 to 1.2 hours, following the morning and evening dose on both the first day of administration and at steady state. The peak plasma concentrations of esomeprazole are higher at steady state compared to on first day of dosing of naproxen and esomeprazole magnesium delayed-release tablets. Figure 1 represents the pharmacokinetics of naproxen and esomeprazole following administration of naproxen and esomeprazole magnesium delayed-release tablets 500 mg/20 mg. Figure 1: Mean plasma concentrations of naproxen and esomeprazole following single dose administration of