title: Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients.
abstract: In 2003, the uricosuric drug benzbromarone was withdrawn from the market. The first alternative drug of choice was the xanthine oxidase inhibitor allopurinol. The purpose was to (1) investigate the efficacy of allopurinol (standard dosage) compared with previous treatment with benzbromarone; and (2) investigate the combination therapy allopurinol-probenecid as an effective alternative treatment compared with previous benzbromarone treatment. A prospective, open study was carried out in a cohort of 51 gout patients who discontinued benzbromarone therapy because of market withdrawal. Patients were given 200-300 mg allopurinol (stage 1). When allopurinol failed to attain the target serum urate (sUr) levels <or=0.30 mmol/l, probenecid 1,000 mg/day was added (stage 2). Treatment with benzbromarone monotherapy (range: 100-200 mg/day; mean 138 mg/day) resulted in 92% of patients reaching target levels sUr <or= 0.30 mmol/l with a decrease of 61[11]% compared to baseline. In stage 1, 32 patients completed treatment with allopurinol monotherapy (range 200-300 mg/day; mean 256 mg/day), which resulted in 25% of patients attaining sUr target levels. Decrease in sUr levels was 36[11]%, which was significantly less compared to treatment with benzbromarone (p < 0.001). In stage 2, 14 patients received allopurinol-probenecid combination therapy, which resulted in 86% of patients attaining target sUr levels (after failure on allopurinol monotherapy), which was comparable to previous treatment with benzbromarone (p = 0.81). Decrease in sUr levels was 53[9]% (CI 95%: 48-58%), which was a non-significant difference compared to previous treatment with benzbromarone (p = 0.23). Benzbromarone is a very effective antihyperuricemic drug with 91% success in attainment of target sUr levels <or=0.30 mmol/l. Allopurinol 200-300 mg/day was shown to be a less potent alternative for most selected patients to attain target sUr levels (13% success). In patients failing on allopurinol monotherapy, the addition of probenecid proves to be an effective treatment strategy for attaining sUr target levels (86% success).
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Medical Centre Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden, The Netherlands. m.reinders@znb.nl
authors.forename: Mattheus K
authors.initials: MK
authors.lastname: Reinders
authors.forename: Eric N
authors.initials: EN
authors.lastname: van Roon
authors.forename: Pieternella M
authors.initials: PM
authors.lastname: Houtman
authors.forename: Jacobus R B J
authors.initials: JR
authors.lastname: Brouwers
authors.forename: Tim L Th A
authors.initials: TL
authors.lastname: Jansen
mesh_terms: D000493:Allopurinol / Q000009:adverse effects / Q000627:therapeutic use*; D001553:Benzbromarone / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006073:Gout / Q000188:drug therapy*; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011339:Probenecid / Q000627:therapeutic use*; D014527:Uric Acid / Q000097:blood* / Q000652:urine; D014528:Uricosuric Agents / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014528:Uricosuric Agents; D014527:Uric Acid; D001553:Benzbromarone; D000493:Allopurinol; D011339:Probenecid