NAPROSYN

Naproxen is rapidly and completely absorbed from the gastrointestinal tract with an in vivo bioavailability of 95%. After administration of naproxen tablets, peak plasma levels are attained in 2 to 4 hours. The elimination half-life of naproxen ranges from 12 to 17 hours. Steady-state levels of naproxen are reached in 4 to 5 days, and the degree of naproxen accumulation is consistent with this half-life.

Naproxen has a volume of distribution of 0.16 L/kg. At therapeutic levels, naproxen is greater than 99% albumin-bound. At doses of naproxen greater than 500 mg/day, there is a less than dose-proportional increase in plasma levels (due to an increase in clearance caused by saturation of plasma protein binding at higher doses). The mean trough concentrations at steady state were 36.5, 49.2 and 56.4 mg/L with the once daily administration of 500, 1000, and 1500 mg of naproxen, respectively. The naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of the maximum naproxen concentration in the plasma (see PRECAUTIONS, Nursing Mothers).

Naproxen is extensively metabolized to 6-O-desmethyl naproxen, and both parent and metabolites do not induce metabolizing enzymes.

The clearance of naproxen is 0.13 mL/min/kg. Approximately 95% of the naproxen from any dose is excreted in the urine, primarily as naproxen (<1%), 6-O-desmethyl naproxen (<1%) or their conjugates (66% to 92%). The plasma half-life of thenaproxen anion in humans ranges from 12 to 17 hours. The corresponding half-lives of both naproxens metabolites and conjugates are shorter than 12 hours, and their rates of excretion have been found to coincide closely with the rate of naproxen disappearance from the plasma. In patients with renal failure metabolites may accumulate (see WARNINGS, Renal Effects).

The combination of naproxen and lansoprazole has not been studied in pediatric patients (see CLINICAL PHARMACOLOGY, PREVACID Special Populations Pediatric Use.)

Studies indicate that the total plasma concentration of naproxen is unchanged in the elderly. The unbound plasma fraction of naproxen is increased in the elderly; however, it represents only < 1% of the total naproxen plasma concentration. Unbound trough naproxen concentrations in elderly subjects have been reported to range from 0.12% to 0.19% of the total naproxen plasma concentration, compared with 0.05% to 0.075% in younger subjects. The clinical significance of this finding is unclear; although, it is possible that the increase in free naproxen concentration could be associated with an increase in the rate of adverse events per a given dosage in some elderly patients.

Pharmacokinetic differences due to race have not been studied.

Naproxen pharmacokinetics has not been determined in subjects with hepatic insufficiency.

Naproxen pharmacokinetics has not been determined in subjects with renal insufficiency. Given that naproxen, its metabolites and conjugates are primarily excreted by the kidney, the potential exists for naproxen metabolites to accumulate in the presence of renal insufficiency (see CLINICAL PHARMACOLOGY, PREVACID Special Populations - Renal Insufficiency.) Elimination of naproxen is decreased in patients with severe renal impairment. Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment ¾ creatinine clearance <30 mL/min ¾ (see WARNINGS, Renal Effects. )

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