A historical journey of searching for uricosuric drugs

Clin Rheumatol. 2022 Jan;41(1):297-305. doi: 10.1007/s10067-021-05930-1. Epub 2021 Sep 28.

Abstract

Gout is an auto-inflammatory disease driven by urate deposits with a second co-stimulatory factor evoking an (peri)arthritic fulminant inflammation often with a debute at night; inflammatory signals are enhanced via a NLRP3 pathway. In gout patients, urate metabolism has had a positive balance for a time period of weeks to years before the arthritic syndrome or tophaecous disease becomes manifest. This may be due to katabolism or weight loss, enhanced dietary affluence, and overweight resulting in increased serum urate levels. Also, a decreased urate excretion results in proneness to hyperuricaemia and clinical gout. Pharmacotherapeutically, a negative urate balance should be the aim of clinicians and then the rational choice of treatment with uricosurics seems quite logical and promising, but has not had a thorough attention of pharma, researchers nor of clinicians, though most gout patients were and still are low excretors. Here, an overview on the 70-year-old journey mankind has made in a search for uricosurics resulting so far in only 1 registered uricosuric per continent.

Keywords: Benzbromarone; Dotinurad; Fractional urate excretion; Probenecid; Uricosuric; Verinurad; Zoxazolamine.

Publication types

  • Review

MeSH terms

  • Aged
  • Gout* / drug therapy
  • Humans
  • Hyperuricemia* / drug therapy
  • Pharmaceutical Preparations*
  • Uric Acid
  • Uricosuric Agents / therapeutic use

Substances

  • Pharmaceutical Preparations
  • Uricosuric Agents
  • Uric Acid

Grants and funding