Rofecoxib (VIOXX, Merck & Co., West Point, PA) is a COX-2-selective inhibitor that combines anti-inflammatory and analgesic efficacy with improved gastrointestinal (GI) safety. The present open-label study investigated the pharmacokinetics, safety, and tolerability of a single, oral dose of rofecoxib (50 mg) in patients with end-stage renal failure (creatinine clearance <5 mL/min/1.73 m(2)) requiring hemodialysis. Rofecoxib AUC(0-48 h), AUC(0- infinity), C(max), T(max), and t(1/2) obtained from renal failure patients on hemodialysis were not significantly different from those obtained from healthy subjects. With hemodialysis initiated 48 hours postdose, rofecoxib AUC(0-48 h) adjusted mean ratio (renal failure/healthy subjects) was 0.81, with a corresponding 90% confidence interval (CI; 0.66, 1.00). Hemodialysis per se had no clinically meaningful effect on rofecoxib pharmacokinetics: plasma rofecoxib concentration-time curves were virtually superimposable when hemodialysis was initiated at 4 or 48 hours following rofecoxib dosing, although mean rofecoxib C(max) was 18% lower during the former (325 versus 395 ng/mL; P = 0.014). Overall, rofecoxib was well tolerated in end-stage renal disease patients. In this study, end-stage renal disease and hemodialysis had little effect on rofecoxib pharmacokinetics. Although there are no clinical data to support the use of rofecoxib in patients with severe renal insufficiency (creatinine clearance, 5-30 mL/min/1.73 m(2)), these data suggest that dosage adjustment of rofecoxib is not needed for patients with impaired renal function.