Naproxen pharmacodynamics

The 2-arylpropionic acid ( profen ) non-steroidal anti-inflammatory drugs, each of which contains a single chiral center, are formulated as racemic (50 50) mixtures of the S(+)- and R(-)-enantiomers, with the exception of naproxen, which is formulated as the S(- -)-enantiomer. Based on inhibition of cyclooxygenase activity, the S(- -)-enantiomer is the eutomer (more potent enantiomer). These drugs differ markedly in both pharmacodynamic activity and pharmacokinetic behavior and, in addition, enantiomer pharmacokinetics of each drug varies among animal species. After intravenous administration of racemic keto-profen to horses, sheep, and 20-week-old calves and measurement of individual enantiomers in plasma, significant differences between the enantiomers were found in systemic clearance in horses and in both systemic clearance and volume of distribution in sheep... 

It has been suggested that the increase in thrombotic cardiovascular events in rofecoxib-treated patients probably represents the antiplatelet effect of naproxen (34,45,46). Naproxen has a long pharmacodynamic half-life and inhibits platelet aggregation by 88% for up to 8 hours (47). 

The pharmacodynamics properties of the propionic acid derivatives (ibuprofen, naproxen, flurbiprofen, fenoprofen, ketoprofen, and oxaprozin) do not differ significantly. All are nonselective cyclooxygenase inhibitors with the effects and side effects common to other tNSAlDs. Although there is considerable variation in their potency as COX inhibitors, this is not of obvious clinical consequence. Some of the propionic acid derivatives, particularly naproxen, have prominent inhibitory effects on leukocyte... 

Holford NHG, Altaian D, Riegelman S, Buskin JN, Upton RA. Pharmacokinetic and pharmacodynamic study of cimetichne administered with naproxen. Clin Pharmacol Ther 9% ) 29, 251-2. 

There appears to be no clinically significant pharmacokinetic or pharmacodynamic interaction between naproxen and zileuton. 

Haematologic In a placebo-controlled, single-blind cross-over study of 3-day cycles separated by washout periods of at least 12 days in 30 healthy individuals, the interaction on antithrombotic effect between acetylsalicylic acid (ASA) and nsNSAIDs (including naproxen 500 mg twice daily, ibuprofen 600 mg daily, meloxicam 15 mg daily and etoricoxib 90 mg daily) taken 2h before ASA (320 mg) was evaluated. Ibuprofen and naproxen inhibited ASA s antithrombocyte effect below the nonresponse threshold. Etoricoxib and meloxicam did not cause relevant changes in ASA thrombocyte inhibition. Naproxen had an inherent weak thrombocyte inhibitory action below the ASA response threshold. This study showed that COX-1 affinity determines the pharmacodynamic interaction between NSAIDs and ASA on the main fxmctions of the thrombocyte adhesion and aggregation. Ibuprofen and also naproxen inhibited ASA s thrombocyte effect... 

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