¹Department of Pharmacokinetics, the Department of Clinical Pharmacology, the Clinical Pharmacology Unit, and the Department of Drug Metabolism, Wyeth-Ayerst Research, and the Division of Nephrology of Graduate Hospital, Philadelphia, Pa and Wyeth-Ayerst Research, Princeton, N.J.

Correspondence: Joseph P. Boni, PhD, 145 King of Prussia Road, Radnor, PA 19087.

^*Supported by Wyeth-Ayerst Research, Philadelphia, Pa.

Presented at the 1993 Meeting of the American Association of Pharmaceutical Scientists, November 14–18, Orlando, Fla.

Received 1 April 1996; Accepted 27 August 1996.

Abstract

Objectives: To compare the pharmacokinetics of bromfenac among normal subjects and renally compromised patients and patients with end-stage renal disease.

Methods: Bromfenac pharmacokinetics were examined after a single 50 mg oral dose in 18 subjects with normal kidney function, 12 subjects with decreased kidney function, and 10 dialysis-dependent subjects. Protein binding was assessed by equilibrium dialysis.

Results: Mean peak concentrations and areas under the concentration versus time curve ranged from 3.3 to 3.9 g/ml and 5.1 to 6.9 g hr/ml, respectively. The mean unbound fraction in the subjects receiving dialysis (0.29%) was nearly twice that in the subjects with normal kidney function (0.17%) and in the subjects with impaired kidney function (0.16%), but no differences were detected in clearance, volume of distribution, or their free fraction-corrected counterparts. Bromfenac half-life nearly doubled in the impaired and dialysis groups but was shorter than the anticipated 8-hour dose interval. Eight subjects had a total of 11 study events; none were serious and all were self-limited.

Conclusions: These findings suggest that no dosage adjustment is necessary in patients with impaired kidney function, but clinical monitoring appropriate for their individual condition is recommended.