Single- and Multiple-Dose Pharmacokinetics of Etoricoxib, a Selective Inhibitor of Cyclooxygenase-2, in Man

The single‐ and multiple‐dose pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase‐2, were examined in two clinical studies. Single‐dose pharmacokinetics—including dose proportionality, absolute bioavailability of the highest dose‐strength (120‐mg) tablet, and the effect of a high...

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Bibliographic Details
Published in:	Journal of clinical pharmacology Vol. 43; no. 3; pp. 268 - 276
Main Authors:	Agrawal, Nancy G. B., Porras, Arturo G., Matthews, Catherine Z., Rose, Mark J., Woolf, Eric J., Musser, Bret J., Dynder, Andrea L., Mazina, Katherine E., Lasseter, Kenneth C., Hunt, Thomas L., Schwartz, Jules I., McCrea, Jacqueline B., Gottesdiener, Keith M.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-03-2003 SAGE Publications Sage Science Wiley Subscription Services, Inc
Subjects:	Adult Area Under Curve Biological and medical sciences Biological Availability Bones, joints and connective tissue. Antiinflammatory agents Cross-Over Studies Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors - administration & dosage Cyclooxygenase Inhibitors - adverse effects Cyclooxygenase Inhibitors - pharmacokinetics Dietary Fats Dose-Response Relationship, Drug Drug Administration Schedule Etoricoxib Fasting Female Food-Drug Interactions Humans Isoenzymes - antagonists & inhibitors Male Medical sciences Membrane Proteins Middle Aged Pharmacology. Drug treatments Prostaglandin-Endoperoxide Synthases Pyridines - administration & dosage Pyridines - adverse effects Pyridines - pharmacokinetics Sulfones - administration & dosage Sulfones - adverse effects Sulfones - pharmacokinetics Tablets Time Factors Human Prostaglandin-endoperoxide synthase Healthy subject Etoricoxib Enzyme Single dose Oral administration Enzyme inhibitor Controlled therapeutic trial Bioavailability Food drug interaction Dose activity relation Non steroidal antiinflammatory agent Multiple dose Oxidoreductases Pharmacokinetics
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Summary:	The single‐ and multiple‐dose pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase‐2, were examined in two clinical studies. Single‐dose pharmacokinetics—including dose proportionality, absolute bioavailability of the highest dose‐strength (120‐mg) tablet, and the effect of a high‐fat meal on the bioavailability of that tablet—were investigated in a two‐part, open, balanced crossover study in two panels of healthy subjects (12 per panel). Steady‐state pharmacokinetics were investigated in an open‐label study in which 24 healthy subjects were administered 120‐mg single and multiple (once daily for 10 days) oral doses of etoricoxib tablets. The pharmacokinetics of etoricoxib were found to be consistent with linearity through doses at least twofold greater than the highest anticipated clinical dose of 120 mg. Etoricoxib administered as a tablet was rapidly and completely absorbed and available; the absolute bioavailability was estimated to be 100%. A high‐fat meal decreased the rate of absorption without affecting the extent of absorption of etoricoxib; therefore, etoricoxib can be dosed irrespective of food. Steady‐state pharmacokinetics of etoricoxib, achieved following 7 days of once‐daily dosing, were found to be reasonably predicted from single doses. The accumulation ratio averaged 2.1, and the corresponding accumulation t1/2 averaged 22 hours, supporting once‐daily dosing. Etoricoxib was generally well tolerated.
Bibliography:	istex:E2012B3F4D44E10EC9DB73F5AA7E6866F6731910 ArticleID:JCPH55 ark:/67375/WNG-PQCS8J7T-K Study funded by grants from Merck & Co., Inc.
ISSN:	0091-2700 1552-4604
DOI:	10.1177/0091270003251122