Tuesday, March 18, 2008

Drug Insight: Cyclo-Oxygenase-2 Inhibitors–A Critical Appraisal

COX2 inhibitors currently in use are the sulfonamide celecoxib, the methylsulfone etoricoxib and the phenylacetic acid legal instrument lumiracoxib.
Of these, celecoxib is the only COX2 inhibitor available in the US.
Another COX2 inhibitor, marketed in the European Labor union for communication of postoperative pain, is parecoxib, an injectable prodrug of valdecoxib.

Pharmacological data of COX2 inhibitors used for oral discussion of arthritic pain are compiled in Assemblage 1 .
Differences in physicochemical characteristics are reflected in different pharmacokinetic demeanor.
Accordingly, the nonacidic compounds celecoxib and etoricoxib distribute homogenously in the body whereas the acidic lumiracoxib, like other acetic acid derivatives (e.g., diclofenac), distributes unequally to prototype in liquid body substance, inflamed tissue paper, kidney and somebody. Owing to its very high lipophilicity, the organic process of celecoxib is relatively slow and incomplete; this chemical undergoes considerable commencement pass metabolization (20–60% oral bioavailability) and its rate of liquidation (t1/2 = 6–12 h approx.) seems to be highly variable quantity. Etoricoxib is eliminated from the body slowly (t1/2 = 20–26 h approx.) and is absorbed at a fast rate, which seems to campaign its fast operation of legal proceeding.

Of the COX2 inhibitors, lumiracoxib has peculiar pharmacodynamic and pharmacokinetic features, which include having the highest selectivity towards COX2 in vitro and the shortest pharmacological half life (t1/2 = 2–6 h approx.).
Lumiracoxib, living thing an amphiphilic material, persists for a long time in the synovial matter, which might explain the long-lasting efficacy of this drug; patients with rheumatoid arthritis treated with lumiracoxib at 400 mg once daily for 7 days had approximately 3-fold higher steady-state concentrations of lumiracoxib in synovial matter as compared with extracellular fluid. As these kinetics of statistical distribution are likely to extend the therapeutic proceeding of lumiracoxib beyond that expected from calcedony pharmacokinetics, the data supporting the use of lumiracoxib in a once-daily regimen for the handling of rheumatoid arthritis.
Administering lumiracoxib at 400 mg, however, exceeds considerably the dose necessary to inhibit COX2 at the time of maximal ECF industriousness, implying that the long-lasting analgesic upshot of lumiracoxib at therapeutic doses, administered once a day, might also be because governance of the drug at high doses translates into extended pharmacodynamic half life.

All COX2 inhibitors undergo oxidative drug metabolic process by cytochrome P450 (CYP) enzymes.
Celecoxib has been shown to inhibit the biological process of the CYP2D6 indigenous language metoprolol, a widely used β-blocker. This action might also interfere with the liquidation of other CYP2D6 substrates, including sedatives, serotonin reuptake inhibitors, tricyclic antidepressants, and some neuroleptics.
For lumiracoxib the study metabolic pathways involve oxidation of the 5-methyl mathematical group, or hydroxylation of its dihaloaromatic ring, or both.
National leader metabolites of lumiracoxib in blood plasma are the 5-carboxy, 4′-hydroxy and 4′-hydroxy-5-carboxy derivatives, of which only the 4′-hydroxy derived function is chemical agent and COX2 selective (about one one-third of its being compound).

On the supposal of their diverse pharmacokinetics, use of different COX2 inhibitors in different clinical settings is recommended.
Accordingly, the slow concentration and variable star low pass metabolization of celecoxib limits its service program for intervention of acute pain.
By range, etoricoxib seems promising for this data point particularly when prolonged natural process is required as in gouty arthritis and rheumatoid arthritis.
This is a part of article Drug Insight: Cyclo-Oxygenase-2 Inhibitors–A Critical Appraisal Taken from "Generic Arcoxia (Etoricoxib)" Information Blog

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