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Diflunisal: a review of pharmacokinetic and pharmacodynamic properties, drug interactions, and special tolerability studies in humans.

Abstract 
1 In the fasting state, peak plasma levels of diflunisal were achieved within 2 hours. The drug was not metabolized and almost totally excreted in the urine as unchanged or conjugated drug. The terminal plasma half-life was approximately 8 hours. These results support a twice daily dose regimen. 
 
2 During multiple dose administration the time required to achieve steady-state plasma levels varied with the dose. A dose regimen of 125 mg twice daily required 2-3 d, whereas a regimen of 500 mg twice daily required 7-9 d to reach a steady-state plasma level. 
 
3 Clinically effective doses of diflunisal decreased the urinary excretion of the major prostaglandin E metabolite, 7α-hydroxy-5,11-diketotetranorprostane-1,16-dioic acid, and exhibited significant uricosuric activity. These same doses did not seem to cause tinnitus, nor did they significantly alter gastrointestinal blood loss, affect blood glucose, bleeding time, or platelet function. 
 
4 Clinically significant drug interactions may be anticipated during concomitant administration with at least one oral anticoagulant (acenocoumarol), but probably not anticipated during the coadministration of oral antidiabetic agents, thiazide diuretics, and non-steroidal anti-inflammatory/analgesic agents. 
 
5 Clinical and laboratory data accumulated during these studies indicated that diflunisal was well tolerated.