PMID- 17999057
OWN - NLM
STAT- MEDLINE
DCOM- 20080715
LR  - 20220408
IS  - 0031-6970 (Print)
IS  - 0031-6970 (Linking)
VI  - 64
IP  - 3
DP  - 2008 Mar
TI  - Clinical use and pharmacological properties of selective COX-2 inhibitors.
PG  - 233-52
AB  - 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 For this reason, two coxibs were withdrawn from the market.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.
FAU - Shi, Shaojun
AU  - Shi S
AD  - Dr. Margarete Fischer-Bosch-Institut fur Klinische Pharmakologie, Auerbachstrasse 
      112, 70376, Stuttgart, Germany.
FAU - Klotz, Ulrich
AU  - Klotz U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20071113
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - 0 (Sulfonamides)
RN  - 0 (Sulfones)
RN  - 144O8QL0L1 (Diclofenac)
RN  - JCX84Q7J1L (Celecoxib)
RN  - V91T9204HU (lumiracoxib)
RN  - WRX4NFY03R (Etoricoxib)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Arthritis, Rheumatoid/drug therapy
MH  - Celecoxib
MH  - Cyclooxygenase 2 Inhibitors/adverse effects/pharmacokinetics/*therapeutic use
MH  - Diclofenac/adverse effects/analogs & derivatives/pharmacokinetics/therapeutic use
MH  - Drug Monitoring
MH  - Etoricoxib
MH  - Humans
MH  - Osteoarthritis/drug therapy
MH  - Pain/drug therapy
MH  - Pyrazoles/adverse effects/pharmacokinetics/therapeutic use
MH  - Pyridines/adverse effects/pharmacokinetics/therapeutic use
MH  - Sulfonamides/adverse effects/pharmacokinetics/therapeutic use
MH  - Sulfones/adverse effects/pharmacokinetics/therapeutic use
RF  - 225
EDAT- 2007/11/14 09:00
MHDA- 2008/07/17 09:00
CRDT- 2007/11/14 09:00
PHST- 2007/08/02 00:00 [received]
PHST- 2007/10/09 00:00 [accepted]
PHST- 2007/11/14 09:00 [pubmed]
PHST- 2008/07/17 09:00 [medline]
PHST- 2007/11/14 09:00 [entrez]
AID - 10.1007/s00228-007-0400-7 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2008 Mar;64(3):233-52. doi: 10.1007/s00228-007-0400-7. Epub 
      2007 Nov 13.