代谢halofantrine均等的代谢物,desbutylhalofantrine,减少当口服酮康唑进行管理。

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邱SM,波特JH,爱德华兹GA,查曼WN

代谢halofantrine均等的代谢物,desbutylhalofantrine,减少当口服酮康唑进行管理。

J制药科学。1998年12月,87 (12):1538 - 41。doi: 10.1021 / js980185w。

PubMed ID

10189263 (在PubMed

]

文摘

Halofantrine(高频)是一个高度亲脂性的抗疟与贫穷和不稳定的吸收。公布的数据表明,高频的口服生物利用度提高三倍的狗在人类和十二次,餐后服用;然而,活跃的比例形成desbutyl代谢物(desbutylhalofantrine间歇)减少人类的2.4倍和6.8倍的狗(弥尔顿et al ., Br。j .中国。杂志。1989年,28岁,71 - 77;Humberstone et al ., j .制药。Sci。1996、85、525 - 529)。目前的研究进行证实的假定的CYP3A4参与N-dealkylation高频的间歇和管理高频有或没有酮康唑(KC),特定的CYP3A4抑制剂,测量产生的等离子体浓度的高频和单位。等离子体单位/高频AUC (0 - 72 h)比高频禁食口服后没有KC是0.56,而禁食后比口服和KC是小于0.05。很可能是肝和prehepatic (enterocyte-based) CYP3A4导致新陈代谢的高频口服后间歇。 Interestingly, the low plasma Hfm/Hf AUC ratios observed after fasted administration of Hf with KC were similar to the low values previously observed when Hf was administered postprandially (despite increased Hf absorption). The mechanism(s) by which postprandial administration of Hf led to a decrease in its metabolism are unknown, but based on the current data, could include inhibition of CYP3A4-mediated metabolism by components of the ingested meal. Other possibilities include a lipid-induced postprandial recruitment of intestinal lymphatic transport or avoidance of metabolism during transport through the enterocyte into the portal blood. Further studies are required to determine the relative contributions by which these different processes may decrease the presystemic metabolism of Hf.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
Halofantrine	细胞色素P450 3 a4	蛋白质	人类	未知的	底物	细节