Naproxen pharmacokinetics and molecular data

Pharmacokinetics
Absorption Distribution Metabolism Pediatric patients Geriatric patients Renal insufficiency

Absorption
After administration of Naproxen tablets, peak plasma levels are attained in 2 to 4 hours. After oral administration of Naproxen sodium tablets, peak plasma levels are attained in 1 to 2 hours. The difference in rates between the two products is due to the increased aqueous solubility of the sodium salt of Naproxen used in Naproxen sodium tablets. Return to top

Distribution
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 less than proportional increase in plasma levels due to an increase in clearance caused by saturation of plasma protein binding at higher doses (average trough Css 36.5, 49.2 and 56.4 mg/L with 500, 1000 and 1500 mg daily doses of Naproxen, respectively). The Naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum Naproxen concentration in plasma. Return to top

Metabolism
Naproxen is extensively metabolized in the liver to 6-O-desmethyl Naproxen, and both parent and metabolites do not induce metabolizing enzymes. Both Naproxen and 6-O-desmethyl Naproxen are further metabolized to their respective acylglucuronide conjugated metabolites. Return to top

Excretion
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 the Naproxen anion in humans ranges from 12 to 17 hours. The corresponding half-lives of both Naproxen's 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. Small amounts, 3% or less of the administered dose, are excreted in the feces. In patients with renal failure metabolites may accumulate. Return to top

Pediatric patients
In pediatric patients aged 5 to 16 years with arthritis, plasma Naproxen levels following a 5 mg/kg single dose of Naproxen suspension were found to be similar to those found in normal adults following a 500 mg dose. The terminal half-life appears to be similar in pediatric and adult patients. Pharmacokinetic studies of Naproxen were not performed in pediatric patients younger than 5 years of age. Pharmacokinetic parameters appear to be similar following administration of Naproxen suspension or tablets in pediatric patients. Return to top

Geriatric patients
Studies indicate that although total plasma concentration of Naproxen is unchanged, the unbound plasma fraction of Naproxen is increased in the elderly, although the unbound fraction is < 1% of the total Naproxen concentration. Unbound trough Naproxen concentrations in elderly subjects have been reported to range from 0.12% to 0.19% of total Naproxen 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. Return to top

Renal insufficiency
Naproxen pharmacokinetics have 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. 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 (creatinine clearance < 30 mL/min). Return to top