人细胞色素P450 3 (CYP3A)介导咪达唑仑代谢:试验条件和特定选择的刺激的效果由alpha-naphthoflavone terfenadine和睾酮。

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Maenpaa J,大厅SD,环BJ,斯特罗姆SC, Wrighton SA

人细胞色素P450 3 (CYP3A)介导咪达唑仑代谢:试验条件和特定选择的刺激的效果由alpha-naphthoflavone terfenadine和睾酮。

药物基因学。1998年4月,8 (2):137 - 55。

PubMed ID

10022752 (在PubMed

]

文摘

离子强度的影响,分析成分、alpha-naphthoflavone(曾帮工)terfenadine和睾丸素对人类CYP3A介导咪达唑仑(MDZ) 1 '羟基化(MDZ 1 ' -哦)和4-hydroxylation (MDZ哦)体外检查。Tris-HCl浓度的增加(三)和磷酸钠(PO4)缓冲区不同影响MDZ 1 ' -哦,MDZ哦形成率和不同的影响MDZ新陈代谢由包含CYP3A4和CYP3A4和CYP3A5微粒体。MDZ代谢不受警察丁缓冲浓度时氢过氧化枯烯(CUOOH)作为活性氧的来源。有趣的是,在场的铵离子溶液中葡萄糖6-phosphate脱氢酶被发现抑制MDZ新陈代谢。添加MgCl2 50 mM和氯化钙(5 - 30毫米)没有影响或抑制MDZ新陈代谢,分别。形成MDZ 1 ' -哦从成人和胎儿肝脏微粒体并表示CYP3A4被曾帮工特定选择的刺激(10 microM)。在人类肝细胞,曾帮工刺激MDZ 1 ' -哦形成(100%)。Terfenadine (20 microM)特定选择的刺激MDZ 1 ' -哦形成三羟甲基氨基甲烷(1 - 200毫米)液、PO4(1 - 10毫米)缓冲区高达159%。令人惊讶的是,表示CYP3A4, terfenadine (20 microM)抑制MDZ 1 ' -哦。Terfenadine MDZ 1 (20 microM)几乎没有影响胎儿肝微粒体的形成-哦。 Testosterone (10 and 100 microM) regioselectively stimulated (up to 269%) MDZ 4-OH formation by adult liver microsomes and expressed CYP3A4. Testosterone (100 microM) inhibited (> 40%) MDZ 1'-OH and MDZ 4-OH formation by fetal liver microsomes. With adult liver microsomes, aNF and terfenadine had little effect on the Km for MDZ 1'-OH formation. However, the Km for MDZ 4-OH formation was decreased (up to 94%) by 100 microM testosterone. In the presence of CUOOH, no stimulation of MDZ metabolism was observed by aNF, terfenadine or testosterone in adult liver microsomes. These studies indicate that because assay conditions can substantially alter the catalytic activity of CYP3A, caution should be exerted when extrapolating results between in vitro and in vivo, and when results from different laboratories are compared. Further, these results suggest that the stimulation of CYP3A4 may also occur in vivo and, consequently, may have clinical importance.

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药物酶

药物	酶	类	生物	药理作用	行动
睾酮cypionate	细胞色素P450 3 a4	蛋白质	人类	未知的	底物 抑制剂 诱导物	细节
睾酮enanthate	细胞色素P450 3 a4	蛋白质	人类	未知的	底物 抑制剂 诱导物	细节
睾酮undecanoate	细胞色素P450 3 a4	蛋白质	人类	未知的	底物 抑制剂 诱导物	细节