Naproxen

Naproxen is rapidly and completely absorbed after oral or rectal administration. Its sodium salt is absorbed faster than the free acid, while their pharmacokinetics after absorption are equivalent. Mean peak plasma concentrations across formulations range from 94 to 97.4 mcg/mL. In a five-day study, immediate-release naproxen given as 500 mg every 12 hours and controlled-release naproxen given as 1000 mg every 24 hours had similar 24-hour exposure values of 1446 and 1448 mcg·hour/mL, respectively.⁷ Another study reported 12-hour exposure values of 767 mcg·hour/mL for standard tablets and 845 mcg·hour/mL for enteric-coated tablets.⁸ More than 99% is bound to albumin at therapeutic concentrations, and its volume of distribution is 0.16 L/kg.² Small amounts enter breast milk.² Extensive hepatic metabolism involves phase I demethylation through CYP1A2, CYP2C8, and CYP2C9, followed by phase II conjugation of the parent drug and its metabolites. Acyl glucuronidation involves UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A9, UGT1A10, and UGT2B7; phenolic glucuronidation involves UGT1A1, UGT1A7, UGT1A9, and UGT1A10. Sulfation involves SULT1A1, SULT1B1, and SULT1E1. After oral administration, approximately 95% of naproxen and its metabolites is recovered in urine, with 66-92% recovered as conjugated metabolites and less than 1% as unchanged drug or its demethylated metabolite.² Fecal excretion accounts for less than 5%.⁷ Clearance is 0.13 mL/min/kg, and the elimination half-life is 12-17 hours.²