title: Pharmacokinetics of etoricoxib in patients with renal impairment.
abstract: The effect of renal insufficiency on the pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase-2, was examined in 23 patients with varying degrees of renal impairment (12 moderate [creatinine clearance between 30 and 50 mL/min/1.73 m2], 5 severe [creatinine clearance below 30 mL/min/1.73 m2], and 6 with end-stage renal disease requiring hemodialysis) following administration of single 120-mg oral doses of etoricoxib. Even the most severe renal impairment was found to have little effect on etoricoxib pharmacokinetics. The low recovery of etoricoxib in dialysate (less than 6% of the dose) supports that hemodialysis also has little effect on etoricoxib pharmacokinetics, and binding of etoricoxib to plasma proteins was generally unaffected by renal disease. Single doses of etoricoxib were generally well tolerated by patients with renal impairment. Based on pharmacokinetic considerations, dosing adjustments are not necessary for patients with any degree of renal impairment. However, because patients with advanced renal disease (creatinine clearance below 30 mL/min/1.73 m2) are likely to be very sensitive to any further compromise of renal function, and there is no long-term clinical experience in these patients, the use of etoricoxib is not recommended in patients with advanced renal disease.
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Nancy G B
authors.initials: NG
authors.lastname: Agrawal
authors.forename: Catherine Z
authors.initials: CZ
authors.lastname: Matthews
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Mazenko
authors.forename: Walter F
authors.initials: WF
authors.lastname: Kline
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Woolf
authors.forename: Arturo G
authors.initials: AG
authors.lastname: Porras
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Geer
authors.forename: Peggy H
authors.initials: PH
authors.lastname: Wong
authors.forename: Meehung
authors.initials: M
authors.lastname: Cho
authors.forename: Josee
authors.initials: J
authors.lastname: Cote
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Marbury
authors.forename: Jack W
authors.initials: JW
authors.lastname: Moncrief
authors.forename: Harry
authors.initials: H
authors.lastname: Alcorn
authors.forename: Suzanne
authors.initials: S
authors.lastname: Swan
authors.forename: Marshall R
authors.initials: MR
authors.lastname: Sack
authors.forename: Richard A
authors.initials: RA
authors.lastname: Robson
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Petty
authors.forename: Jules I
authors.initials: JI
authors.lastname: Schwartz
authors.forename: Keith M
authors.initials: KM
authors.lastname: Gottesdiener
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D002986:Clinical Trials as Topic; D016861:Cyclooxygenase Inhibitors / Q000493:pharmacokinetics*; D000077613:Etoricoxib; D005260:Female; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011485:Protein Binding; D011725:Pyridines / Q000493:pharmacokinetics*; D006435:Renal Dialysis; D013450:Sulfones / Q000493:pharmacokinetics*
chemical_list: D016861:Cyclooxygenase Inhibitors; D011725:Pyridines; D013450:Sulfones; D000077613:Etoricoxib