Diflunisal, a new-acting analgesic and prostaglandin inhibitor: effect of concomitant acetylsalicylic acid therapy on ototoxicity and on disposition of both drugs

Abstract

Intermittent and concomitant acetylsalicylic acid (ASA) therapy was superimposed onto a 21-day regimen with diflunisal 250 mg b.i.d. Low doses of ASA (600 mg single dose or 300 mg q.i.d.) did not influence signficantly diflunisal blood levels whereas a 600 mg q.i.d. dosing caused a small significant drop, especially at trough level. This drop is not expected to be clinically significant. No ototoxicity could be demonstrated with any treatment of diflunisal though four of fourteen subjects reported mild tinnitus during concomitant therapy at the higher doses of ASA. Diflunisal at 375 mg b.i.d. failed to alter the metabolism of a single dose of labelled ASA (600 mg) as judged by plasma levels, urinary excretion and plasma binding. Daily urinary excretion of prostaglandins E1 and E2 major metabolite was decreased by about 70% by diflunisal.