双氯芬酸的影响,戒酒硫、伊曲康唑、柚子汁和红霉素奎尼丁的药物动力学。

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Damkier P,汉森,Brosen K

双氯芬酸的影响,戒酒硫、伊曲康唑、柚子汁和红霉素奎尼丁的药物动力学。

Br中国新药杂志。1999年12月,48 (6):829 - 38。

PubMed ID

10594487 (在PubMed

]

文摘

目的:体外研究表明氧化奎尼丁对CYP3A4 3-hydroxyquinidine是一个特定的标记反应活动。评估这个反应的可能使用的体内标记CYP3A4活性,我们研究的参与细胞色素CYP2C9, CYP2E1和CYP3A4奎尼丁的体内氧化代谢。方法:一个开放的30只健康的年轻男性志愿者进行了研究。一个200毫克口服剂量的药物动力学研究了奎尼丁之前和期间的日常管理100毫克双氯芬酸,CYP2C9底物(n = 6);200毫克戒酒硫,CYP2E1的抑制剂(n = 6);100毫克伊曲康唑,CYP3A4的抑制剂(n = 6);250毫升单一强度葡萄柚汁每天两次,CYP3A4的抑制剂(n = 6);每天250毫克的红霉素4次,CYP3A4的抑制剂(n = 6)。调查其他酶活性、咖啡因(CYP1A2),金雀花碱(CYP2D6),美芬妥因(CYP2C19)、甲苯磺丁脲(CYP2C9)和皮质醇(CYP3A4)也进行了研究。结果:伴随管理双氯芬酸部分间隙N-oxidation奎尼丁的减少了27%,而没有发现影响奎尼丁的其他药代动力学参数。 Concomitant administration of disulfiram did not alter any of the pharmacokinetic parameters of quinidine. Concomitant administration of itraconazole reduced quinidine total clearance, partial clearance by 3-hydroxylation and partial clearance by N-oxidation by 61, 84 and 73%, respectively. The renal clearance was reduced by 60% and the elimination half-life increased by 35%. Concomitant administration of grapefruit juice reduced the total clearance of quinidine and its partial clearance by 3-hydroxylation and N-oxidation by 15, 19 and 27%, respectively. The elimination half-life of quinidine was increased by 19%. The caffeine metabolic index was reduced by 25%. Concomitant administration of erythromycin reduced the total clearance of quinidine and its partial clearance by 3-hydroxylation and N-oxidation by 34, 50 and 33%, respectively. Cmax was increased by 39%. CONCLUSIONS: The results confirm an important role for CYP3A4 in the oxidation of quinidine in vivo, and this applies particularly to the formation of 3-hydroxyquinidine. While a minor contribution of CYP2C9 to the N-oxidation of quinidine is possible, a major involvement of the CYP2C9 or CYP2E1 enzymes in the oxidation of quinidine in vivo is unlikely.

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药物酶

药物	酶	类	生物	药理作用	行动
金雀花碱	细胞色素P450 2 d6	蛋白质	人类	未知的	底物 抑制剂	细节