Diflunisal dosing

Platelet function Platelet function and bleeding time are inhibited by diflunisal at higher doses. 

Urine alkalinization is a treatment modality that increases elimination of poisons by the intravenous administration of sodium bicarbonate to produce urine with a pH of more than or equal to 7.5 and must be supported by high urine flow. This technique might be useful for the elimination of drugs with an acid pKa such as salicylates (but not recommended for phenobarbital intoxication for which multiple-dose activated charcoal is better), chlorpropamide, 2,4-dichlorophenoyacetic acid, diflunisal, fluoride, mecoprop, methotrexate. Complications include severe alkalemia, hypokalemia, hypocalcemia and coronary vasoconstriction. 

Peak plasma concentrations are reached within 2 to 3 h after oral dosing. Diflunisal is heavily bound to plasma protein (>99 %), has a long elimination half-life (8-12 h) and non-linear kinetics. Hence, it is used with an initial loading dose (1000 mg) and a lower maintenance dose (500-1000 mg/day). Diflusinal is excreted as glucuronide in the urine. 

Diflunisal 500 mg superior to aspirin, but has slower onset and longer duration initial 1,000-mg dose shortens time to onset... 

Diflunisal (dolobid) is a difluorophenyl derivative of salicylic acid (Figure 26-1). It is almost completely absorbed after oral administration, and peak plasma concentrations occur within 2-3 hours. It is extensively bound to plasma albumin (99%). About 90% of the drug is excreted as glucuronide conjugates, and its rate of elimination is dose-dependent. At the usual analgesic dose (500-750 mg/day), the plasma averages 8-12 hours. Diflunisal appears in the milk of lactating women. 

The drug has been used primarily as an analgesic in the treatment of osteoarthritis and musculoskeletal strains or sprains in these circumstances it is about three to four times more potent than aspirin. The usual initial dose is 500-1000 mg, followed by 250-500 mg every 8-12 hours. For rheumatoid arthritis or osteoarthritis, 250-500 mg is administered twice daily maintenance dosage should not exceed 1.5 g/day. Diflunisal does not produce auditory side effects and appears to cause fewer and less intense GI and antiplatelet effects than aspirin. 

Aspirin 600 mg four times daily caused a 15% reduction in the plasma levels of diflunisal 250 mg twice daily for 3 days. Single-dose studies have shown that the absorption of nabumetone 1 g is not significantly altered by aspirin 1.5 g. The plasma levels of tolmetin 1.2 g daily were slightly reduced by aspirin 3.9 g daily. ... 

The clearance of a single 250-mg dose of diflunisal was 53% higher in 6 women taking oral contraceptives than in 6 control women, but was similar to the clearance in 6 men. This difference is unlikely to be of clinical importance. 

Valproate toxicity developed in three patients given large and repeated doses of aspirin. Increased levels of free valproate were found in S children within hours of them taking aspirin. Con-versefy, a slightly reduced valproate level was reported in one patient who took ibuprofen. Modestly altered protein binding has been shown when sodium valproate was given with diflunisal or naproxen, but this appears unlikely to be clinically important... 

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