摘要
目的 研究参与双环醇代谢的主要药物代谢酶及代谢动力学参数,分离鉴定双环醇代谢产物。方法 双环醇与大鼠和人肝微粒体进行温孵,以高效液相色谱、质谱、核磁共振技术检测并分离鉴定双环醇及其代谢产物。结果 双环醇在地塞米松诱导大鼠肝微粒体中的代谢速率显著高于正常大鼠肝微粒体,酮康唑可显著抑制双环醇的代谢。双环醇主要代谢产物为: 4 羟基 4′ 甲氧基 6 羟甲基 6′ 甲氧羰基 2, 3, 2′, 3′ 双亚甲二氧基联苯和 4 甲氧基 4′ 羟基 6 羟甲基 6′ 甲氧羰基 2, 3, 2′, 3′ 双亚甲二氧基联苯。结论 双环醇在大鼠和人肝微粒体的主要代谢产物为 4 羟基 4′ 甲氧基 6 羟甲基 6′ 甲氧羰基 2, 3, 2′, 3′ 双亚甲二氧基联苯和 4 甲氧基 4′ 羟基 6 羟甲基 6′ 甲氧羰基 2, 3, 2′, 3′ 双亚甲二氧基联苯,细胞色素P450 3A主要参与双环醇代谢。
Aim To study the drug metabolizing enzymes involved in the metabolism of bicyclol and identify the major metabolites of bicyclol in rat and human liver microsomes. Methods Bicyclol was incubated with rat and human liver microsomes. The metabolites of bicyclol were isolated by HPLC and identified by MS and 1H NMR. Results The metabolic rate of bicyclol in DEX-induced rat liver microsomes was obviously higher than that in untreated microsomes, while it was much lower in human liver microsomes. Ketoconazole was capable to exhibit strong inhibition (>90%) on bicyclol metabolism. Two metabolites of bicyclol were identified to be 4-hydroxy-4′-methoxy-6-hydroxy-methyl-6′-methoxycarbonyl-2,3,2′,3′-bis(methylene-dioxy) biphenyl and 4-methoxy-4′-hydroxy-6- hydroxymethyl-6′-methoxycarbonyl-2,3,2′,3′-bis(methylene-dioxy) biphenyl. Conclusion CYP3A was considered as the major catalyst involved in bicyclol metabolism in vitro and two metabolites of bicyclol in rats were identified as 4-hydroxy-4′-methoxy-6-hydroxy-methyl-6′-methoxycarbonyl-2,3,2′,3′-bis(methylene-dioxy) biphenyl and 4-methoxy-4′-hydroxy-6- hydroxymethyl-6′-methoxycarbonyl-2,3,2′,3′-bis(methylene-dioxy) biphenyl.
出处
《药学学报》
CAS
CSCD
北大核心
2005年第2期111-116,共6页
Acta Pharmaceutica Sinica
基金
科技部"九五"国家重点科技攻关计划资助项目 (96 901 01 45)
美国中华医学基金(CMB).
