CYP2D6的影响和CYP3A活动立即释放羟考酮的药物动力学。

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沉着的CF Daali Y,瓦格纳M, Hopfgartner G, Eap CB, Rebsamen MC,罗西MF, Hochstrasser D,天P, Desmeules农协

CYP2D6的影响和CYP3A活动立即释放羟考酮的药物动力学。

Br J杂志。2010年6月,160 (4):907 - 18。doi: 10.1111 / j.1476-5381.2010.00673.x。

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20590587 (在PubMed

]

文摘

背景和目的:高个人间变化的活动摘要酶催化氧化羟考酮的(细胞色素P450 (CYP) 2 d6和3),由于遗传多态性和/或药物之间的相互作用。CYP2D6的影响和/或CYP3A活性的药物动力学调制研究羟考酮仍然不佳。实验方法:随机交叉双盲安慰剂对照研究10健康志愿者对CYP2D6基因分型(6广泛(EM),两个缺陷(PM / IM)和两个超速的代谢(嗯)]。志愿者随机收到在五个不同的场合:羟考酮x 0.2毫克公斤(1)和安慰剂;羟考酮和奎尼丁CYP2D6(抑制剂);羟考酮、酮康唑(CYP3A抑制剂);羟考酮和奎尼丁+酮康唑;安慰剂。血液样本为羟考酮的血浆浓度和代谢物(羟吗啡酮,noroxycodone和noroxymorphone)收集24 h后剂量。与右美沙芬CYP2D6的表现型()和CYP3A(与咪达唑仑)评估在每个会话。 KEY RESULTS: CYP2D6 activity was correlated with oxymorphone and noroxymorphone AUCs and C(max) (-0.71 < Spearman correlation coefficient rhos < -0.92). Oxymorphone C(max) was 62% and 75% lower in PM than EM and UM. Noroxymorphone C(max) reduction was even more pronounced (90%). In UM, oxymorphone and noroxymorphone concentrations increased whereas noroxycodone exposure was halved. Blocking CYP2D6 (with quinidine) reduced oxymorphone and noroxymorphone C(max) by 40% and 80%, and increased noroxycodone AUC(infinity) by 70%. Blocking CYP3A4 (with ketoconazole) tripled oxymorphone AUC(infinity) and reduced noroxycodone and noroxymorphone AUCs by 80%. Shunting to CYP2D6 pathway was observed after CYP3A4 inhibition. CONCLUSIONS AND IMPLICATIONS: Drug-drug interactions via CYP2D6 and CYP3A affected oxycodone pharmacokinetics and its magnitude depended on CYP2D6 genotype.

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药物酶

药物	酶	类	生物	药理作用	行动
羟吗啡酮	细胞色素P450 2 d6	蛋白质	人类	未知的	底物	细节
羟吗啡酮	细胞色素P450 3 a4	蛋白质	人类	未知的	底物	细节