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Pharmacology: Pharmacodynamics: Naproxen sodium is a non-steroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory and antipyretic properties.
Pharmacokinetics: Absorption: Naproxen sodium is absorbed rapidly and completely from the gastrointestinal tract after oral administration.
Concomitant administration of food can delay the absorption of naproxen, but does not affect its extent. Plasma levels and pain relief are achieved within 30 minutes after administration and peak plasma levels are reached in 1-2 hours, depending on the intake of food. Naproxen sodium dissolves primarily in the small bowel rather than the stomach, so the absorption is delayed until the stomach is emptied.
Distribution: The distribution volume of naproxen is 0.16 l/kg. At therapeutic levels, naproxen is greater than 99% albumin-bound. There is less than proportional increase in plasma level at doses more than 500 mg/day due to an increase in clearance caused by saturation of plasma protein binding at higher doses. However, the concentration of unbound naproxen continues to increase proportionally to dose.
Steady-state plasma levels of naproxen are reached after 3-4 days. Naproxen enters synovial fluid, crosses the placenta and has been found in the milk of lactating mothers at a concentration approximately 1% of that found in plasma.
Metabolism: Naproxen sodium is extensively metabolised in the liver to 6-0-desmethyl naproxen.
Elimination: Approximately 95% of the naproxen from any dose is excreted in the urine, primarily as naproxen (less than 1%), 6-0-desmethyl naproxen (less than 1%), or their conjugates (66-92%). The rate of excretion of metabolites and conjugates has been found to coincide closely with the rate of naproxen disappearance from the plasma. Small amounts, 3% or less, are excreted in the faeces. The clearance of naproxen is approximately 0.13 ml/min/kg. The elimination half-life of naproxen is approximately 14 hours and independent of the chemical form or the formulation.
Pharmacokinetics in Special Populations: Renal impairment: Elimination of naproxen is decreased in patients with severe renal impairment due to potential accumulation of naproxen and metabolite in the kidney. The clearance of naproxen is greater than the estimated from the degree of renal impairment alone for patients with severely impaired renal function (creatinine clearance less than 10 ml/min).
Children: In children aged 5 to 16 years, the pharmacokinetic profile of naproxen is similar to that in adults, although the clearance is generally higher in children than in adults.
