细胞色素P450酶导致脱甲基的马普替林人。

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杰特Brachtendorf L, A Beckurts KT Holscher啊,富U

细胞色素P450酶导致脱甲基的马普替林人。

Toxicol杂志》2002年3月,90 (3):144 - 9。

PubMed ID

12071336 (在PubMed

]

文摘

从患者的案例报告四环的抗抑郁药物马普替林,看来这药多态的新陈代谢。因此,我们研究了形成主要的马普替林代谢物desmethylmaprotiline识别人类细胞色素p - 450酶(CYP)。在孵化项目从两个不同的捐赠者,与人类肝微粒体基质马普替林曾在五个不同浓度(5 500 microM)。cyp的选择性抑制奎尼丁(0.5 -50 microM;CYP2D6), furafylline (0.3 -30 microM;CYP1A2),酮康唑(0.2 -20 microM;CYP3A4),美芬妥因(20 - 200 microM;CYP2C19), chlorzoxazone (1 - 100 microM;CYP2E1), sulphaphenazole (0.2 -100 microM;CYP2C9)和香豆素(0.2 -100 microM; CYP2A6) were used. Desmethylmaprotiline concentrations were measured by HPLC, and enzyme kinetic parameters were estimated using extended Michaelis-Menten equations with non-linear regression. Relevant inhibition of the desmethylmaprotiline formation rate was observed in incubations with quinidine, furafylline and ketoconazole only. Formation rates of desmethylmaprotiline were consistent with a two enzyme model with a high (K(M)=71 and 84 microM) and a low (K(M)=531 and 426 microM) affinity site for maprotiline in the two samples, respectively. The high affinity site was competitively inhibited by quinidine (K(i,nc) 0.13 and 0.61 microM), the low-affinity site was non-competitively inhibited by furafylline (K(i,nc) 0.11 and 1.3 microM). Thus it appears that CYP2D6 and CYPIA2 contribute to maprotiline demethylation. Based on the parameters obtained, for plasma concentrations of 1 microM 83% (mean) of desmethylmaprotiline formation in vivo is expected to be mediated by CYP2D6 while 17% only may be attributed to CYPIA2 activity.

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药物酶

药物	酶	类	生物	药理作用	行动
马普替林	细胞色素P450 1 a2	蛋白质	人类	未知的	底物	细节
马普替林	细胞色素P450 2 d6	蛋白质	人类	未知的	底物	细节