RRC ID 52477
著者 Nakamura M, Fujita K, Toyoda Y, Takada T, Hasegawa H, Ichida K.
タイトル Investigation of the transport of xanthine dehydrogenase inhibitors by the urate transporter ABCG2.
ジャーナル Drug Metab Pharmacokinet
Abstract Hyperuricemia induces gout and kidney stones and accelerates the progression of renal and cardiovascular diseases. Adenosine 5'-triphosphate-binding cassette subfamily G member 2 (ABCG2) is a urate transporter, and common dysfunctional variants of ABCG2, non-functional Q126X (rs72552713) and semi-functional Q141K (rs2231142), are risk factors for hyperuricemia and gout. A recent genome wide association study suggested that allopurinol, a serum uric acid-lowering drug that inhibits xanthine dehydrogenase, is a potent substrate of ABCG2. In this study, we aimed to examine the transport of xanthine dehydrogenase inhibitors via ABCG2. Our results show that ABCG2 transports oxypurinol, an active metabolite of allopurinol, whereas allopurinol and febuxostat, a new xanthine dehydrogenase inhibitor, are not substrates of ABCG2. The amount of oxypurinol transported by ABCG2 vesicles significantly increased in the presence of ATP, compared to that observed with mock vesicles. Since the half-life of oxypurinol is longer than that of allopurinol, the xanthine dehydrogenase-inhibiting effect of allopurinol mainly depends on its metabolite, oxypurinol. Our results indicate that the serum level of oxypurinol would increase in patients with ABCG2 dysfunction.
巻・号 33(1)
ページ 77-81
公開日 2018-2-1
DOI 10.1016/j.dmpk.2017.11.002
PII S1347-4367(17)30102-7
PMID 29342419
MeSH ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism* Allopurinol / metabolism* Biological Transport / physiology Cell Membrane / metabolism Enzyme Inhibitors / metabolism HEK293 Cells Hep G2 Cells Humans Hyperuricemia / metabolism Neoplasm Proteins / metabolism* Oxypurinol / metabolism* Xanthine Dehydrogenase / antagonists & inhibitors* Xanthine Dehydrogenase / metabolism*
IF 2.772
引用数 5
リソース情報
ヒト・動物細胞 293(RCB1637)