Characteristics of Naproxen
NPVS. Naproxen – white or almost white, odourless crystalline powder. It is soluble in lipids, practically insoluble in water at low pH, freely soluble in water at high pH. The octanol/water distribution coefficient at pH 7.4 is 1.6-1.8. The molecular weight is 230.26.
Naproxene sodium salt is a crystalline substance of white or cream-white color, freely soluble in water at neutral pH. Molecular weight 252,24.
Pharmacological action – anti-inflammatory, antipyretic, anti-aggregating, analgesic.
Reduces the activity of cyclooxygenase (COH-1 and COH-2), resulting in impaired PG synthesis. After ingestion naproxene and naproxene sodium is quickly and completely absorbed from the gastrointestinal tract, bioavailability – 95%. Cmax in the blood is reached 2-4 hours after taking naproxene and 1-2 hours after taking naproxene sodium. Binding to proteins is 98-99%. The concentration Dmitry Sazonov of naproxene in plasma increases in proportion to the blood dose, while the proportionality is impaired when the single dose of 500 mg is exceeded. T1/2 from plasma – 12-17 hours. Biotransformed into 6-O-demethylnaproxene. The volume of naproxene distribution is 0.16 l/kg, clearance is 0.13 ml/min/kg. The equilibrium concentration of naproxene is achieved after 4-5 days of continuous intake. Approximately 95% is excreted with urine, <1% – in the form of 6-O-demethylnaproxene, <1% – as a constant preparation (66-92% – as their conjugates), <3% – with faeces. In renal insufficiency, metabolites may accumulate.
Concentration in plasma, which is necessary for development of analgesic effect, is achieved faster in the form of sodium salt naproxene than in the form of naproxene.
Limits the development of exudative and proliferative phases of inflammation, has antipyretic effect, inhibits the flow of free-radical reactions. Causes the alleviation or disappearance of pain (including pain in the joints at rest and during movement), reduces morning stiffness and swelling of the joints, increases the volume of movement. The anti-inflammatory effect comes at the end of the first week of treatment.
Carcinogenicity. In a 24-month study in rats at doses of 8, 16 and 24 mg/kg/day (50, 100 and 150 mg/m2) no carcinogenic effect naproxen was detected. The maximum used dose was 0.28 MHRD.
Use of the substance Naproxen Dosage
Inflammatory and degenerative diseases of the musculoskeletal system, including rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, joint syndrome with exacerbation of gout, juvenile rheumatoid arthritis; pain syndrome: neuralgia, myalgia, ossalgia, radiculitis, head and toothache, tendinitis, pain in cancer, postoperative pain syndrome accompanied by inflammation, injuries of the musculoskeletal system and soft tissues, adnexitis, primary dysmenorrhea; pain and fever in infectious and inflammatory diseases of the upper respiratory tract (as part of a comprehensive therapy).
Naproxene Contraindications .
Hypersensitivity, “aspirinic” asthma, “aspirinic” triad (a combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance of acetylsalicylic acid and pyrazolone LV), erosive ulcerative lesions of the gastrointestinal tract in the acute phase, hematopoiesis, hepatic and/or renal failure, children under 1 year old.
Restrictions on use
Expressed heart failure, adolescence (under 16 years).
Application during pregnancy and breastfeeding
Teratogenic effects. In animal reproduction studies, naproxen was administered to rats at doses of 20 mg/kg/day (125 mg/m2/day), approximately equivalent to 0.23 MHRD, to rabbits at 20 mg/kg/day (220 mg/m2/day), or 0.27 MHRD, and to mice at 170 mg/kg/day (510 mg/m2/day), or 0.28 MHRD, and no infertility disturbance or fetal harm was detected.
However, reproductive studies in animals do not always predict effects in humans. Adequate and strictly controlled studies have not been conducted in pregnant women. Use in pregnancy is possible if the expected effects of the therapy exceed the potential risk to the fetus.