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-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.
Agrawal
Nancy G B
NG
Department of Drug Metabolism, WP75-200, Merck Research Laboratories, West Point, PA 19486, USA.
Porras
Arturo G
AG
Matthews
Catherine Z
CZ
Rose
Mark J
MJ
Woolf
Eric J
EJ
Musser
Bret J
BJ
Dynder
Andrea L
AL
Mazina
Katherine E
KE
Lasseter
Kenneth C
KC
Hunt
Thomas L
TL
Schwartz
Jules I
JI
McCrea
Jacqueline B
JB
Gottesdiener
Keith M
KM
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004041:Dietary Fats; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000077613:Etoricoxib; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013607:Tablets; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004041:Dietary Fats; D007527:Isoenzymes; D008565:Membrane Proteins; D011725:Pyridines; D013450:Sulfones; D013607:Tablets; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000077613:Etoricoxib