卡维地洛与一些常用化学药的体外葡醛酸化代谢性相互作用

In Vitro Metabolic Interaction between Carvedilol and Some Commonly Used Drugs

目的研究卡维地洛与一些常用化学药的葡醛酸化代谢性相互作用，为临床合理用药提供科学依据。方法选择42种临床上可能合用的药物与卡维地洛在鼠肝微粒体中共孵育。以HPLC测定孵育液中卡维地洛葡醛酸结合物的浓度，计算共孵育药物对卡维地洛2个葡醛酸结合物的IC50或Ki值。结果非洛地平，拉西地平，尼群地平，辛伐他汀和洛伐他汀对卡维地洛葡醛酸化代谢均有较强的体外抑制作用，Ki值在0．65～63．48μmol·L^-1之间。这5种药物对卡维地洛葡醛酸结合物M1的Ki值均低于对M2的Ki值，对M1的抑制作用强于对M2的抑制作用。其中拉西地平对M1和M2的抑制作用最强，Ki值分别约0．65和6．44μmol·L^-1。结论这5种药物对卡维地洛葡醛酸化代谢有较强的体外抑制作用，在联合用药时应引起注意。

OBJECTIVE To study the metabolic drug interactions of carvedilol with some commonly used chemical drugs for providing some usefill information for clinic. METHODS Carvedilol was co-incubated with 42 commonly used drugs in rat liver microsomes and the concentrations of carvedilol glucuronides were determined by HPLC. The IC50 or Ki were calculated. RESULTS Felodipine, lacidipine, nitrendipine, simvastatin and lovastatin showed fairly strong inhibition on the glucuronidation of carvedilol in vitro, with Ki value between 0. 65 - 63. 48 μmol·L^-1. The Ki values of the five drugs for carvedilol glucuronide M1 were lower than those for carvedilol glucuronide M2, as evidence of stronger inhibition for M1. Among these five drugs, lacidipine had the strongest inhibition, with the Ki value about 0. 65 μmol·L^-1 and 6. 44 μmol·L^-1 for M1 and M2, respectively. CONCLUSION There were strong interactions between the five drugs and carvedilol in vitro glucuronidation, the special attention should be paid when being co-administrated.