Name: Diflunisal (Dolobid)
Class: Salicylate.
Mechanism: Inhibition of cyclooxygenase ® inhibition of prostaglandin synthesis. Also inhib. of PMN adhesion, aggregation, & activation (ramifications uncertain).
Absorption: Oral. Absorbed from stomach and upper intestine. Peak conc. 2-3 hr.
Dist.: Weak acid (pKa <5). ~90% protein binding. Vd @ albumin Vd. No CNS.
Metabolism.: 1° = liver. Phase I (oxid.) & Phase II (conjug.).
Excretion, t½: Metabolismolites in urine. Renal failure ® retention of glucuronide Metabolismolites®potential for toxic accumulation of orig. compound. t½ = 11-15 hr. Clearance decreased w/renal impairment & in the elderly.
Toxicity/S.E.s: GI—esophagitis & esophageal strictures; gastroduodenal erosions, ulceration, hemorrhage, & perforation; ileal inflammation, strictures, hemorrhage, & perforation; colon hemorrhage and exacerbation of inflammatory bowel disease. Hypersensitivity—possible cross-reaction w/aspirin. Inhib. of platelet aggregation. Kidney—Na+ retention, hemodynamic renal failure, interstitial nephritis. CNS—dizziness, tinnitus, headache, aseptic meningitis. Overdose—Acute is less serious than w/aspirin, but may cause Metabolismolic acidosis & seizures.
Utility: Treat pain, inflammation, dysmenorrhea, patent ductus arteriosis, acute gout.