This study will evaluate the effects of the new anti-inflammatory drug, Celebrex, on
relieving pain after oral surgery. It is also designed to assess the drug's selective
inhibition of a chemical called cyclooxygenase-2 and not its closely related form,
cyclooxygenase-1. This selective inhibition allows pain alleviation without the adverse
side effects (e.g., bleeding and stomach upset) often associated with anti-inflammatory
Healthy volunteers who require removal of their third molars are eligible for this study.
Participants will have oral surgery for tooth extraction after receiving a local anesthetic
(lidocaine) in the mouth and a sedative (midazolam) through an arm vein. On the evening
before and 1 hour before surgery, patients will be given a dose of either the standard
anti-inflammatory drug ibuprofen (Advil, Nuprin, Motrin), or Celebrex, or a placebo (a pill
with no active ingredient). After surgery, a small piece of tubing will be placed in each
extraction site and tied to an adjacent tooth to hold it in place. Samples will be
collected from the tubing to measure chemicals involved in pain and inflammation. Patients
will stay in the clinic for up to 6 hours after surgery while the anesthetic wears off and
will complete pain questionnaires. During that time, they may receive acetaminophen plus
codeine (Tylenol 3), if needed, for pain. The tubing then will be removed and the patient
discharged with standard pain medication.
Prostanoids are mediators that have been implicated in all stages of inflammation. The
inhibition of prostanoid synthesis by NSAIDs forms the basis of their therapeutic as well as
side effects. NSAIDs directly inhibit cyclooxygenase [COX], which leads to reduction of
prostaglandin synthesis and also to gastric erosions, inhibition of platelet aggregation and
nephrotoxicity. The identification of the two isoforms of COX lead to the hypothesis that
COX-2 is responsible for the production of prostaglandins following tissue injury, while
COX-1 is involved in normal homeostasis.
The selective COX-2 inhibitors are believed to be efficacious anti-inflammatory drugs devoid
of the side effects associated with the inhibition of COX-1. However, the selectivity of
these drugs has only been demonstrated in vitro and ex vivo, which may not be a reliable
indicator of the in vivo selectivity. The proposed study aims to evaluate the in vivo
selectivity of celecoxib, a drug demonstrated to be a selective inhibitor of COX-2 in vitro
in the oral surgery model of acute inflammation.
Healthy volunteers between the ages of 18-65 years.
Patients will be eligible for this study if the two mandibular molars are classified as
partial or full bony impactions.
Patients who are allergic to sulfa-drugs.
Patients who have had asthma, hives or an allergic reaction to aspirin, ibuprofen or any
Patients with gastrointestinal ulcers or a history of gastrointestinal bleeding.
Patients who are pregnant or nursing.
Patients of infection or inflammation [pericoronitis] at either extraction site.
Patients with severe kidney disease.
Patients who are taking any of the following drugs: anti-depressants, diuretics, aspirin
on a near daily basis, coumadin or other blood thinners.
Patients who are taking drugs known to inhibit P450 2C9 and drugs metabolized by P450 2D6.