Synopsis: Benzbromarone is a benzofuran derivative which lowers serum urate and increases urinary urate excretion in normal, hyperuricaemic and gouty subjects. In open short- and long-term studies benzbromarone reduced serum uric acid levels by one-third to one-half and maintained its effectiveness for periods of up to 8 years. Single-dose experimental studies have shown benzbromarone to have a urate-lowering effect similar to that of a therapeutic dose of probenecid or sulphinpyrazone, but unlike these drugs benzbromarone can be administered in a once daily regimen. In 2 short-term comparative therapeutic trials in a small number of patients with hyperuricaemia, 80mg of micronised benzbromarone daily was at least as effective as 1000mg of probenecid or 300mg of allopurinol daily in lowering serum uric acid levels. Side-effects during benzbromarone administration are usually mild and primarily gastrointestinal in nature.

Pharmacodynamic Studies: In studies in rats, benzbromarone decreased the reabsorption of uric acid injected into the proximal tubule but had no effect on excretion of distally-injected urate. In man, therapeutic doses of benzbromarone reduced serum uric acid levels in normal or hyperuricaemic individuals by one-third to one-half, with a concurrent rise in urinary uric acid excretion. In addition to uricosuric activity, an effect on enzymes involved in purine metabolism and an increase in faecal urate excretion have been proposed as the mechanisms of the lowering effect of benzbromarone on serum uric acid. Some urate-lowering effect has occurred in a small number of anephric patients, supporting the possible existence of an extrarenal mechanism of action. Further systematic studies are needed however, to confirm this. A dose of 80mg of micronised or 100mg of non-micronised benzbromarone has about the same effect on serum urate and urinary urate excretion as 1 to 1.5g of probenecid or 400 to 800mg of sulphinpyrazone. The duration of activity of a single dose is up to 48 hours and benzbromarone can thus be administered in a once daily dose, unlike other uricosuric drugs.

As with other uricosuric agents, concomitant administration of pyrazinamide or aspirin decreases the effectiveness of benzbromarone, but studies of the extent of this decrease in activity have produced variable results, depending on the dosages of the inhibiting drugs.

Pharmacokinetic Studies: Absorption of benzbromarone after oral dosing is affected by the particle size of the preparation administered; 100mg of a standard non-micronised dose showing the same bioavailability as about 80mg of micronised drug. About 50% of a single, non-micronised dose is absorbed and dehalogenated in the liver to form bromobenzarone and benzarone, which retain part of the activity of the parent compound. Excretion occurs primarily via the bile and faeces and to a lesser extent in the urine.

Therapeutic Trials: Although benzbromarone has undergone only limited direct comparative trials with other uricosuric agents, it is nevertheless an effective urate-lowering drug. In open studies, serum uric acid levels have been decreased by one-third to one-half in hyperuricaemic and gouty patients and maintained at the lower levels for periods of up to 8 years. Most tophaceous deposits either disappeared or were reduced in size after several months of therapy. In 2 short-term comparative studies, 80mg of micronised benzbromarone daily was at least as effective as 1000mg of probenecid or 300mg of allopurinol daily in lowering serum uric acid levels of a smaller number of patients with …