临床药物动力学和代谢氯喹。关注最近的进步。
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Ducharme J, Farinotti R
临床药物动力学和代谢氯喹。关注最近的进步。
Pharmacokinet。1996年10月,31 (4):257 - 74。doi: 10.2165 / 00003088-199631040-00003。
- PubMed ID
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8896943 (在PubMed]
- 文摘
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介绍了知识的当前状态对氯喹的性格,特别强调立体选择性和微粒体代谢。此外,病人的physiopathological状态的影响和民族起源氯喹药物动力学进行了探讨。在人类中,氯喹multiexponentially浓度下降。卷的药物广泛分布,分布的200 - 800 L /公斤计算从等离子体浓度和200 L /公斤估计从全血数据时(浓度高5到10倍)。氯喹与血浆蛋白是60%,同样通过肾脏和肝脏。政府氯喹后迅速脱烷烃通过细胞色素P450 (CYP)到酶药物活性desethylchloroquine bisdesethylchloroquine。Desethylchloroquine和bisdesethylchloroquine浓度达到40 - 10%的氯喹的浓度,分别;氯喹和desethylchloroquine浓度下降缓慢,消除半衰期20至60天。父药物和代谢物可在尿液中发现几个月后单个剂量。在体外和体内,氯喹和desethylchloroquine竞争性抑制CYP2D1/6-mediated反应。 Limited in vitro studies and preliminary data from clinical experiments and observations point to CYP3A and CYP2D6 as the 2 major isoforms affected by or involved in chloroquine metabolism. In vitro efficacy studies did not detect any difference in potency between chloroquine enantiomers but, in vivo in rats, S(+)-chloroquine had a lower dose that elicited 50% of the maximal effect (ED950) than that of R(-)-chloroquine. Stereoselectivity in chloroquine body disposition could be responsible for this discrepancy. Chloroquine binding to plasma proteins is stereoselective, favouring S(+)-chloroquine (67% vs 35% for the R-enantiomer). Hence, unbound plasma concentrations are higher for R(-)-chloroquine. Following separate administration of the individual enantiomers, R(-)-chloroquine reached higher and more sustained blood concentrations. The shorter half-life of S(+)-chloroquine appears secondary to its faster clearance. Blood concentrations of the S(+)-forms of desethylchloroquine always exceeded those of the R(-)-forms, pointing to a preferential metabolism of S(+)-chloroquine.
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- 药物
- 药物反应
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反应 细节
