58 - Parecoxib  pp. 245-248

Parecoxib

By Jeff Gudin and Despina Psillides

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Generic Name: parecoxib

Trade/Proprietary Name: Dynastat™ (available in EU)

Manufacturer: Pfizer Inc.

Drug class: COX-2 selective inhibitor

Chemical Structure: see Figure 58.1

Chemical Formula: C19H18N2O4S; molecular wt 370

Introduction

Parecoxib is unique in that it is the first COX-2-specific inhibitor that can be parenterally administered. This feature of parecoxib allows for its role in pre-operative and post-operative analgesia when patients are often unable to take oral pain medications. Parecoxib has a long history in the literature, which will be reviewed below. However, it must be stated that parecoxib is not FDA-approved in the USA, but is available in other countries for short-term peri-operative analgesia.

Parecoxib, N-{[4-(5-methyl-3-phenylisoxazol-4-yl)phenyl]sulfonyl}propanamide, is an inactive prodrug of valdecoxib. After injection, either intramuscular or intravenous, parecoxib rapidly undergoes hepatic metabolism, predominantly via cytochromes P450 3A4 and P450 2C9, to valdecoxib. The peak plasma concentration of valdecoxib occurs 30 minutes after IV and 60 minutes after IM injection of parecoxib. Parecoxib is 100% bioavailable, and is renally excreted in the urine, with 70% as inactive metabolites. The half-life of parecoxib is approximately 22 minutes as opposed to 8 hours for valdecoxib.

Parecoxib and the other COX-2 inhibitors may provide anti-inflammatory effects while still maintaining gastrointestinal integrity and normal platelet functioning. The cyclooxygenases, both COX-1 and COX-2, lead to the production of prostaglandins. The difference between the two forms is that they are expressed at different times and in different cellular locations.

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