TY - JOUR
T1 - In vivo selectivity of a selective cyclooxygenase 2 inhibitor in the oral surgery model
AU - Khan, Asma A.
AU - Brahim, Jaime S.
AU - Rowan, Janet S.
AU - Dionne, Raymond A.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - Objective: Prostanoids formed by cyclooxygenase play an important role in pain and the induction of inflammation. It is generally believed that COX-1 is constitutively expressed, whereas COX-2 is primarily inducible during inflammation. This study examined the in vivo selectivity of celecoxib, a COX-2 inhibitor, and evaluated whether estimates of selectivity that are based on in vitro and ex vivo analyses are reliable indicators of in vivo selectivity. Methods: Subjects (103 outpatients undergoing surgical removal of two impacted mandibular third molars) received either 200 mg celecoxib, 600 mg ibuprofen, or placebo 8 hours before surgery and a second dose 1 hour before surgery. After surgery, microdialysis probes were placed in the surgical sites for collection of inflammatory transudate. Samples were collected every 20 minutes and pain intensity was estimated concurrently with a visual analog scale and a categorical rating scale for up to 4 hours after surgery. Results: A significant analgesic effect (P <. 01, compared with placebo) was shown for both drugs, with the efficacy of celecoxib being intermediate between ibuprofen and placebo. A similar relationship was observed for the suppression of prostaglandin E2 (a product of both isoforms) at time points consistent with COX-2 expression (P <. 001). Ibuprofen consistently suppressed thromboxane B2 (a product of COX-1) levels at all time points (P <. 05), whereas the effect of celecoxib did not differ from that of placebo. Conclusions: The suppression of products of COX-2 coincident with pain suppression and the absence of COX-1 inhibition suggest that celecoxib is a relatively selective COX-2 inhibitor in vivo.
AB - Objective: Prostanoids formed by cyclooxygenase play an important role in pain and the induction of inflammation. It is generally believed that COX-1 is constitutively expressed, whereas COX-2 is primarily inducible during inflammation. This study examined the in vivo selectivity of celecoxib, a COX-2 inhibitor, and evaluated whether estimates of selectivity that are based on in vitro and ex vivo analyses are reliable indicators of in vivo selectivity. Methods: Subjects (103 outpatients undergoing surgical removal of two impacted mandibular third molars) received either 200 mg celecoxib, 600 mg ibuprofen, or placebo 8 hours before surgery and a second dose 1 hour before surgery. After surgery, microdialysis probes were placed in the surgical sites for collection of inflammatory transudate. Samples were collected every 20 minutes and pain intensity was estimated concurrently with a visual analog scale and a categorical rating scale for up to 4 hours after surgery. Results: A significant analgesic effect (P <. 01, compared with placebo) was shown for both drugs, with the efficacy of celecoxib being intermediate between ibuprofen and placebo. A similar relationship was observed for the suppression of prostaglandin E2 (a product of both isoforms) at time points consistent with COX-2 expression (P <. 001). Ibuprofen consistently suppressed thromboxane B2 (a product of COX-1) levels at all time points (P <. 05), whereas the effect of celecoxib did not differ from that of placebo. Conclusions: The suppression of products of COX-2 coincident with pain suppression and the absence of COX-1 inhibition suggest that celecoxib is a relatively selective COX-2 inhibitor in vivo.
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U2 - 10.1067/mcp.2002.125560
DO - 10.1067/mcp.2002.125560
M3 - Article
C2 - 12152003
AN - SCOPUS:0036331458
VL - 72
SP - 44
EP - 49
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 1
ER -