Solvo Biotechnology, Szeged, Hungary.
Drug Metab Pharmacokinet. 2012;27(3):349-53. doi: 10.2133/dmpk.dmpk-11-nt-068. Epub 2011 Nov 29.
We are showing that chlorothiazide, a diuretic, is an ABCG2 substrate. It is a Biopharmaceutics Classification System/Biopharmaceutics Drug Distribution and Classification System (BCS/BDDCS) Class IV drug with low bioavailability. Therefore, we tested if chlorothiazide interacts with major apically located intestinal efflux transporters. Our data show that chlorothiazide is transported by ABCG2 with a Km value of 334.6 µM and does not interact with ABCB1 or ABCC2. The chlorothiazide-ABCG2 interaction results in a vectorial transport in MDCKII-BCRP and Caco-2 cells with efflux ratios of 36 and 8.1 respectively. Inhibition of ABCG2 in Caco-2 cells reduced the efflux ratio to 1.4, suggesting that ABCG2 plays a role in limiting chlorothiazide bioavailability in humans.
我们发现利尿剂氯噻嗪是 ABCG2 的底物。它是一种生物药剂学分类系统/生物药剂学药物分布和分类系统（BCS/BDDCS）分类为 IV 类的药物，其生物利用度较低。因此，我们测试了氯噻嗪是否与主要位于肠道顶侧的外排转运蛋白相互作用。我们的数据表明，氯噻嗪由 ABCG2 转运，Km 值为 334.6 µM，并且不与 ABCB1 或 ABCC2 相互作用。氯噻嗪与 ABCG2 的相互作用导致 MDCKII-BCRP 和 Caco-2 细胞中的载体转运，其外排比分别为 36 和 8.1。在 Caco-2 细胞中抑制 ABCG2 将外排比降低至 1.4，表明 ABCG2 在外排氯噻嗪的生物利用度方面在人体中发挥作用。
