REVIEW - Clinical use and pharmacological properties of selective COX-2 inhibitors

December 22, 2008

Eur J Clin Pharmacol. 2008 Mar;64(3):233-52. Epub 2007 Nov 13.

Clinical use and pharmacological properties of selective COX-2 inhibitors.

Shi S, Klotz U.

Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie,

Auerbachstrasse 112, 70376, Stuttgart, Germany.

Selective COX-2 inhibitors (coxibs) are approved for the relief of

acute pain and symptoms of chronic inflammatory conditions such as

osteoarthritis (OA) and rheumatoid arthritis (RA). They have similar

pharmacological properties but a slightly improved gastrointestinal

(GI) safety profile if compared to traditional nonsteroidal

anti-inflammatory drugs (tNSAIDs). However, long-term use of coxibs

can be associated with an increased risk for cardiovascular (CV)

adverse events (AEs). For this reason, two coxibs were withdrawn from

the market. Currently celecoxib, etoricoxib, and lumiracoxib are used.

These three coxibs differ in their chemical structure and selectivity

for COX-2, which might explain some of their pharmacological features.

Following oral administration, the less lipophilic celecoxib has a

lower bioavailability (20-40%) than the other two coxibs (74-100%).

All are eliminated by hepatic metabolism involving mainly CYP2C9

(celecoxib, lumiracoxib) and CYP3A4 (etoricoxib). Elimination

half-life varies from 5 to 8 h (lumiracoxib), 11 to 16 h (celecoxib)

and 19 to 32 h (etoricoxib). In patients with liver disease, plasma

levels of celecoxib and etoricoxib are increased about two-fold.

Clinical efficacies of the coxibs are comparable to tNSAIDs. There is

an ongoing discussion about whether the slightly better GI

tolerability (which is lost if acetylsalicylic acid is coadministered)

of the coxibs is offset by their elevated risks for CV AEs (also seen

with tNSAIDs other than naproxen), which apparently increase with dose

and duration of exposure. In addition, the higher costs for coxibs (if

compared to tNSAIDs, even when a " gastroprotective " proton pump

inhibitor is coadministered) should be taken into consideration, if a

coxib will be selected for certain patients with a high risk for GI

complications. For such treatment, the lowest effective dose should be

used for a limited time. Monitoring of kidney function and blood

pressure appears advisable. It is hoped that further controlled

studies can better define the therapeutic place of the coxibs.

PMID: 17999057

Not an MD

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