Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0018099 (
gout
)
5,192
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Although allopurinol has been available for approximately 50 years, hyperuricemia and its sequelae are not only prevalent, but the incidence and costs associated with this disorder continue to increase. However, several new therapies have been developed. Recombinant urate oxidase has been useful in the treatment of tumor lysis hyperuricemia, and pegylated urate oxidase shows promise in patients with hyperuricemia and
gout
. Febuxostat and
Y-700
are new oral xanthine oxidase inhibitors that are in human clinical trials. Tailoring of antilipid therapy in selected hyperuricemic and hyperlipidemic patients with fenofibrate may be of benefit in lowering blood cholesterol and uric acid levels. Similarly, treatment of selected hyperuricemic patients who also are hypertensive with losartan or amlodipine may be beneficial in lowering blood pressure and hyperuricemia. Despite these advances, new treatments for hyperuricemia are needed.
...
PMID:Serum uric acid-lowering therapies: where are we heading in management of hyperuricemia and the potential role of uricase. 1513 5
Y-700
, a novel xanthine oxidase inhibitor, was recently developed for the treatment of hyperuricemia and
gout
. Since the major elimination route of this compound is hepatic metabolism and excretion, the aim of the present study was to characterize the uptake mechanism of
Y-700
in the liver, which is also the pharmacological target of
Y-700
. Efficient uptake of
Y-700
was observed both in the liver in vivo and in isolated rat hepatocytes. The uptake was Na(+)-dependent, saturable and inhibited both by ATP-depressants and various organic anions. Indomethacin competitively inhibited
Y-700
uptake, whereas the inhibitory effect of organic cations and nucleosides was not so remarkable. Saturable and Na(+)-dependent uptake of
Y-700
was also observed in freshly isolated human hepatocytes. Uptake of
Y-700
by sinusoidal membrane transporters, such as organic anion transporter (Oat) 2 and organic anion transporting polypeptide (OATP)-B, OATP-C, OATP-8, and Oatp1, could not be detected although uptake of
Y-700
in the oocytes expressing sodium/taurocholate cotransporting polypeptide (NTCP) was slightly observed. In conclusion, active transport system(s), which specifically recognize certain types of anionic compounds, are involved in the hepatic uptake of
Y-700
and, at least partially, relevant to its elimination from the circulation as well as delivery to pharmacological target.
...
PMID:Carrier-mediated hepatic uptake of a novel nonrenal excretion type uric acid generation inhibitor, Y-700. 1636 28
