Đăng xuất
Pharmacotherapeutic groups: Propionic acid derivatives. ATC code: M01AE02.
Pharmacology: Pharmacodynamics: Naproxen is a racemic non-steroidal anti-inflammatory analgesic that belongs to propionic acid derivatives. The pharmacological activity of naproxen is considered to lie with the S enantiomer, which is the sole enantiomer in the clinically used naproxen, and it is based on the inhibition of cyclooxygenase enzymes and prostaglandin synthesis. Naproxen reduces fever through inhibition of central prostaglandin synthesis and alleviates inflammation and pain by inhibiting peripheral prostaglandin synthesis, which in turn reduces the release of mediators that intensify pain and inflammation. The effects of naproxen on protective mechanisms in the gastric mucosa, renal perfusion, and platelets are also due to prostaglandin synthesis inhibition.
Pharmacokinetics: Following oral administration, naproxen is absorbed completely (95-100%). In connection with food intake, absorption slows down but bioavailability remains unaffected. Following administration of a single dose of 250 mg (25 mg/mL, 10 mL) to healthy adults, the peak plasma concentration is achieved in 1 to 1.5 hours, and the peak concentration is about 50 microg/mL. The therapeutic plasma concentration is considered to be 30-90 mcg/mL. Plasma protein binding of naproxen is extensive (>99%); it binds mainly to albumin but also to globulins, and its distribution volume is about 0.15 L/kg. The total naproxen concentration in synovial fluid is 65-7% from that in plasma, whereas the concentrations of unbound naproxen are the same. Naproxen has linear pharmacokinetics with single doses of up to 500 mg. At doses higher than this, plasma protein binding is saturated, the concentration of unbound naproxen increases, and elimination is accelerated.
The elimination half-life in plasma is 12-15 hours and in synovial fluid up to 30 hours.
Naproxen is eliminated in the liver (CYP450 isoenzymes 1A2, 2C8, and 2C9) into pharmacologically inactive 6-O-demethylnaproxen. Naproxen and 6-O-demethylnaproxen are excreted mainly in the urine as sulfate and glucuronide conjugates. Enterohepatic circulation apparently exists but its degree is not known. Only 1-2% of the total dose is excreted in the feces. Pharmacokinetics of naproxen in children and adults are the same whereas in the elderly the plasma concentrations of unbound naproxen are higher and elimination slower. Naproxen is not accumulated to a significant degree in connection with renal failure. Naproxen is not dialysable. If creatinine clearance is less than 10 mL/min, 6-odemethylnaproxen is accumulated but it can be eliminated in hemodialysis. In connection with hepatic failure, the elimination of naproxen slows down, and if plasma albumin concentrations decrease, plasma concentrations of unbound naproxen increase.
