Primaquine metabolism by human liver microsomes: effect of other antimalarial drugs.
Primaquine metabolism by human liver microsomes: effect of other antimalarial drugs.
复制标题
人肝微粒体对伯氨喹的代谢：其他抗疟药物的作用。
DOI：
10.1016/0006-2952(92)90453-p
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发表时间：
1992
影响因子：
5.8
通讯作者：
D. Back
中科院分区：
文献类型：
--
作者：
K. N. Bangchang;J. Karbwang;D. Back
研究了多种药物对抗疟药伯氨喹在人肝微粒体（N = 4）体外代谢的影响。唯一的代谢物经色谱鉴定为羧基伯氨喹。酮康唑是一种已知的细胞色素P450同工酶抑制剂，其ic50和kik值分别为15 μM和6.7 μM，对羧基伯氨的形成有明显的抑制作用。这一发现以及代谢物形成对NADPH的依赖性表明，细胞色素P450同工酶催化了代谢物的产生。在实际或可能与伯氨喹共同用于疟疾患者的化合物中，只有甲氟喹产生抑制作用（Ki= 52.5μM）。奎宁、蒿甲醚、青蒿琥酯、氟茴香碱和氯喹对代谢物的形成没有明显的抑制作用。甲氟喹或其他抗疟药物与伯氨喹同时服用似乎不太可能导致明显的性情改变。
A number of drugs have been studied for their effect on the metabolism of the antimalarial drug primaquine by human liver microsomes (N = 4)in vitro. The only metabolite generated was identified as carboxyprimaquine by co-chromatography with the authentic standard. Ketoconazole, a known inhibitor of cytochrome P450 isozymes, caused marked inhibition of carboxyprimaquine formation withic50andKivalues of 15 and 6.7 μM, respectively. This finding and the dependency of metabolite formation on NADPH indicates that cytochrome P450 isozyme(s) catalysed metabolite production. Of compounds actually or likely to be coadministered with primaquine to malaria patients, only mefloquine produced any inhibition (Ki= 52.5μM). Quinine, artemether, artesunate, halofantrine and chloroquine did not significantly inhibit metabolite formation. It seems unlikely that the concurrent administration of mefloquine, or other antimalarials, with primaquine will lead to appreciably altered disposition.