Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1    Pharmacodynamic properties
Pharmacotherapeutic group:
ATC code: M01AX17

Nimesulide is a non-steroidal anti-inflammatory drug with analgesic and antipyretic properties which acts as an inhibitor of prostaglandin synthesis enzyme cyclo-oxygenase.

Pharmacokinetic Properties

5.2    Pharmacokinetic properties

Nimesulide is well absorbed when given per o.s. After a single dose of 100mg nimesulide a peak plasma level of 3-4 mg/L is reached in adults after 2-3 hours. AUC = 20 - 35 mg h/L. No statistically significant difference has been found between these figures and those seen after 100mg given twice daily for 7 days.

Up to 97.5% binds to plasma proteins.

Nimesulide is extensively metabolised in the liver following multiple pathways, including cytochrome P450 (CYP) 2C9 isoenzymes. Therefore, there is the potential for a drug interaction with concomitant administration 
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of drugs which are metabolised by CYP2C9 (see under section 4.5). The main metabolite is the para-hydroxy derivative which is also pharmacologically active. The lag time before the appearance of this metabolite in the circulation is short (about 0.8 hour) but its formation constant is not high and is considerably lower than the absorption constant of nimesulide. Hydroxynimesulide is the only metabolite found in plasma and it is almost completely conjugated. T½ is between 3.2 and 6 hours.

Nimesulide is excreted mainly in the urine (approximately 50% of the administered dose).
Only 1-3% is excreted as the unmodified compound. Hydroxynimesulide, the main metabolite, is found only as a glucuronate. Approximately 29% of the dose is excreted after metabolism in the faeces.

The kinetic profile of nimesulide was unchanged in the elderly after acute and repeated doses.

In an acute experimental study carried out in patients with mild to moderate renal impairment (creatinine clearance 30-80 ml/min) versus healthy volunteers, peak plasma levels of nimesulide and its main metabolite were not higher than in healthy volunteers. AUC and t1/2 beta were 50% higher, but were always within the range of kinetic values observed with nimesulide in healthy volunteers. Repeated administration did not cause accumulation.
Nimesulide is contra-indicated in patients with hepatic impairment (see section 4.3).