PHARMACOKINETICS OF OXICAM NONSTEROIDAL ANTIINFLAMMATORY AGENTS

Oxicam nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of st ructurally closely related substances with anti-inflammatory, analgesi c and antipyretic activities. They have a weakly acidic character and are extensively bound to plasma proteins. Piroxicam, the most widely u sed oxicam, is well absorbed after oral administration. Peak plasma co ncentrations (C-max) of the drug are reached within 2 to 4 hours. Piro xicam has a small volume of distribution and a low plasma clearance. I t undergoes hepatic metabolism and only 5 to 10% is excreted unchanged in urine. The elimination half-life varies between 30 and 70 hours. A ge of the patient and renal or hepatic dysfunction do not seem to have any major effect on the pharmacokinetics of piroxicam. The drug reduc es the renal excretion of lithium to a clinically significant extent, but the clinical significance of piroxicam-aspirin (acetylsalicylic-ac id) and piroxicam-acenocoumarol interaction has not been established. Ampiroxicam, droxicam and pivoxicam are prodrugs of piroxicam that hav e been synthesised to reduce piroxicam-related gastrointestinal irrita tion. All prodrugs are well absorbed, but C-max values are reached lat er than those following administration of piroxicam. Tenoxicam is used in the management of rheumatic and inflammatory diseases. Mean C-max values are achieved 2 hours postdose. Food reduces the rate but not th e extent of absorption. The oral bioavailability of tenoxicam is 100% and rectal bioavailability is 80%. Like piroxicam, tenoxicam has a low volume of distribution and low plasma clearance. It is eliminated thr ough hepatic metabolism. The mean elimination half-life is 60 to 75 ho urs. The pharmacokinetics of tenoxicam are independent of patient age, or concurrent liver or renal diseases. High doses of aspirin have bee n shown to increase the elimination of tenoxicam, but this has little clinical significance. Isoxicam was in widespread clinical use until i ts worldwide marketing was suspended because of fatal skin reactions. Isoxicam is completely absorbed, but C-max values are not reached unti l 10 hours postdose. It has a low plasma clearance, approximately 5 ml /min (0.3 L/h), and low volume of distribution. The mean elimination h alf-life is 30 hours and does not appear to be affected by the age of the patient. Isoxicam potentiated the anticoagulant effect of warfarin , necessitating a 20% dosage reduction. Lornoxicam differs from other oxicam NSAIDs because it has a short elimination half-life of 3 to 4 h ours. On the basis of limited data, some individuals seem to eliminate lornoxicam very slowly, suggesting the presence of polymorphic metabo lism. The pharmacokinetics of cinnoxicam and sudoxicam have not been s tudied thoroughly. However, like other oxicams, they appear to be abso rbed completely after oral administration. Although the development of sudoxicam was stopped because of frequent adverse effects, this drug is interesting because, unlike other oxicams, its appears to have nonl inear elimination pharmacokinetics.