ulodesine and Hyperuricemia

To update recent developments in medications targeting hyperuricemia, but not including medications recently labelled in the European Union and the United States.. A new xanthine oxidase inhibitor, Topiloric (Fujiyakuhin Co., Ltd. Japan) Uriadec (Sanwa Kagaku Kenkyusho Co., Ltd. Japan), has been developed and labelled in Japan. An inhibitor of purine nucleoside phosphorylase, Ulodesine, is in development in combination with allopurinol. The rest of the medications in the pipeline for hyperuricemia are targeting renal transporters of uric acid, mainly URAT1 and OAT4, acting as uricosuric agents. Most of them, such as lesinurad and arhalofenate, are being tested in trials in combination with allopurinol and febuxostat. The most potent RDEA3170 is being tested in monotherapy, but also associated with febuxostat. Recently, medications showing dual activity, inhibiting both xanthine oxidoreductase and URAT1, have been communicated or started exploratory clinical trials. There is no report of medications targeting other transporters such as Glut9 or ABCG2.. There are a number of medications in the pipeline targeting hyperuricemia, mostly uricosurics in combination with xanthine oxidase inhibitors, but some targeting both xanthine oxidoreductase and URAT1. Increasing the number of available medications will ensure proper control of hyperuricemia to target serum urate levels in the near future for most, if not all, patients with hyperuricemia.

Topics: Acetamides; Drug Design; Gout; Gout Suppressants; Humans; Hyperuricemia; Imino Furanoses; Molecular Targeted Therapy; Phenylacetates; Pyrimidinones; Thioglycolates; Triazoles; Uricosuric Agents

The uric acid metabolism pathway is more similar in primates and humans than in rodents. However, there are no reports of using primates to establish animal models of hyperuricaemia (HUA).. To establish an animal model highly related to HUA in humans.. Inosine (75, 100 and 200 mg/kg) was intraperitoneally administered to adult male rhesus monkeys (. Inosine (200 mg/kg) effectively increased the SUA level in rhesus monkeys from 51.77 ± 14.48 at 0 h to 178.32 ± 14.47 μmol/L within 30 min and to peak levels (201.41 ± 42.73 μmol/L) at 1 h. PNP mRNA level was increased, whereas XO mRNA and protein levels in the liver were decreased by the inosine group compared with those in the control group. No changes in mRNA and protein levels of the renal uric acid transporter were observed. Ulodesine, allopurinol and febuxostat eliminated the inosine-induced elevation in SUA in tested monkeys.. An acute HUA animal model with high reproducibility was induced; it can be applied to evaluate new anti-HUA drugs

Topics: Acute Disease; Allopurinol; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Febuxostat; Hyperuricemia; Imino Furanoses; Inosine; Macaca mulatta; Male; Pyrimidinones; Reproducibility of Results; Uric Acid