Glucuronidation双氢青蒿素含量测定的体内,由人类肝脏微粒体和UDP-glucuronosyltransferases表示。
文章的细节
-
引用
复制到剪贴板 -
Ilett KF, Ethell BT,马格斯杰,戴维斯TM,古怪的KT, Burchell B,阿萍TQ,星期四le助教,挂数控,Pirmohamed M,公园BK,爱德华G
Glucuronidation双氢青蒿素含量测定的体内,由人类肝脏微粒体和UDP-glucuronosyltransferases表示。
药物金属底座Dispos。2002年9月30日(9):1005 - 12所示。doi: 10.1124 / dmd.30.9.1005。
- PubMed ID
-
12167566 (在PubMed]
- 文摘
-
本研究的目的是阐明双氢青蒿素含量测定的代谢途径(DHA),青蒿素衍生物青蒿琥酯的活性代谢物(艺术)。尿液收集来自17个越南的成人恶性疟疾曾获得120毫克的艺术注射。和代谢产物的高效液相色谱-光谱法分析了(HPLC-MS)。人类的肝脏微粒体孵化了[12 - (3)H] DHA和代数余子式glucuronidation或细胞色素P450-catalyzed氧化。人类肝细胞溶质孵化与代数余子式硫酸盐化作用。HPLC-MS代谢物进行检测和/或高效液相色谱法与放射化学检测。新陈代谢的DHA重组人类UDP-glucuronosyltransferases (ugt)进行了研究。HPLC-MS尿液分析确定alpha-DHA-beta-glucuronide (alpha-DHA-G)和产品特征为四氢呋喃alpha-DHA-G异构体。DHA是现在只有很少量。四氢呋喃异构体的比例,alpha-DHA-G高度变量(中位数0.75;范围0.09 - -64)。 Nevertheless, alpha-DHA-G was generally the major urinary product of DHA glucuronidation in patients. The tetrahydrofuran isomer appeared to be at least partly a product of nonenzymic reactions occurring in urine and was readily formed from alpha-DHA-G by iron-mediated isomerization. In human liver microsomal incubations, DHA-G (diastereomer unspecified) was the only metabolite found (V(max) 177 +/- 47 pmol min(-1) mg(-1), K(m) 90 +/- 16 microM). Alpha-DHA-G was formed in incubations of DHA with expressed UGT1A9 (K(m) 32 microM, V(max) 8.9 pmol min(-1) mg(-1)) or UGT2B7 (K(m) 438 microM, V(max) 10.9 pmol mg(-1) min(-1)) but not with UGT1A1 or UGT1A6. There was no significant metabolism of DHA by cytochrome-P450 oxidation or by cytosolic sulfotransferases. We conclude that alpha-DHA-G is an important metabolite of DHA in humans and that its formation is catalyzed by UGT1A9 and UGT2B7.
beplay体育安全吗DrugBank数据引用了这篇文章
- 药物
- 药物酶
-
药物 酶 类 生物 药理作用 行动 青蒿琥酯 UDP-glucuronosyltransferase 1 - 9 蛋白质 人类 未知的底物细节 青蒿琥酯 UDP-glucuronosyltransferase 2 b7 蛋白质 人类 未知的底物细节 - 药物反应
-
反应 细节
