INHIBITION OF METOPROLOL METABOLISM BY CHLOROQUINE AND OTHER ANTIMALARIAL-DRUGS
INHIBITION OF METOPROLOL METABOLISM BY CHLOROQUINE AND OTHER ANTIMALARIAL-DRUGS
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DOI：
10.1111/j.2042-7158.1990.tb05405.x
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发表时间：
1990-04-01
影响因子：
3.3
通讯作者：
LENNARD, MS
中科院分区：
文献类型：
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作者：
LANCASTER, DL;ADIO, RA;LENNARD, MS
在大鼠和人中，研究了一系列抗疟药损害美托洛尔代谢的能力。氯喹在大鼠肝微粒体中是有效的抑制剂（美托洛尔α的Ki值-羟基化= 0.18 μ M，O-去甲基化= 0.36 μ M）。其他抗疟药也抑制美托洛尔氧化。奎宁的效力与氯喹相似，而奎尼丁、伯氨喹和甲氟喹的效力略差。氯喹也抑制人肝微粒体中的美托洛尔氧化，尽管其效力比大鼠低约两个数量级，并且损伤程度在个体肝脏之间差异很大。麻醉大鼠腹腔注射氯喹可降低美托洛尔（40 mg酒石酸盐kg-1 i. p.）的清除率。在2.5、4.0、25和40 mg kg-1剂量下，分别为对照值的54、34、20和26%。我们的结论是，抗疟治疗可能有助于以前报道的美托洛尔的代谢模式之间的高加索人和高加索人的差异。
The ability of a series of antimalarial drugs to impair the metabolism of metoprolol in rat and man has been examined. Chloroquine was a potent inhibitor in rat liver microsomes (Ki value for metoprolol .alpha.-hydroxylation = 0.18 .mu.M and for O-demethylation = 0.36 .mu.M). The other antimalarial drugs also inhibited metoprolol oxidation. Quinine was similar to chloroquine in potency, while quinidine, primaquine and mefloquine were slightly less potent. Chloroquine also inhibited metoprolol oxidation in human liver microsomes, although it was about two orders of magnitude less potent than in the rat and the extent of impairment varied greatly between individual livers. Intraperitoneal administration of chloroquine to anaesthetized rats decreased the clearance of metoprolol (40 mg tartrate salt kg-1 i.p.) to 54, 34, 20 and 26% of the control value at doses of 2.5, 4.0, 25 and 40 mg kg-1, respectively. We conclude that antimalarial treatment might have contributed to a previously reported difference in the metabolic pattern of metoprolol between Caucasians and Nigerians.