摘要
目的体外研究巴马香猪、人和大鼠肝微粒体中洛伐他汀代谢的酶动力学差异,并用人体肝微粒体细胞色素P450 3A(CYP3A)酶特异性抑制剂酮康唑(KCZ)进行抑制,观察抑制活性反应的差异,评估巴马香猪作为人体CYP3A酶代谢药物研究实验动物模型的可行性。方法制备巴马香猪、人和大鼠的肝微粒体,构建肝微粒体与洛伐他汀的反应体系以及抑制剂抑制反应体系,利用RP-HPLC测定洛伐他汀代谢的变化,并对其相应活性值进行比较。结果巴马香猪肝微粒体代谢洛伐他汀的酶动力学变化比大鼠更为与人体相似。人体CYP3A特异性抑制剂均可以显著抑制三者的代谢,但是巴马香猪代谢速率下降程度与人体接近。结论巴马香猪与大鼠相比,更适用于作为人CYP3A酶代谢的相关药物研究的良好动物模型。
Objective To evaluate the feasibility of Bama miniture pigs to be used as a model on pharmacokenetic properties of CYP3A by comparing enzyme kinetics of lovastatin metabolism in liver microsomes of Bama miniture pigs, humans and rats. Methods Liver microsomes were prepared from Bama miniature pigs, humans and rats, respectively. To evaluate the biotransformation activity in the minipig liver microsomes and compare with those of humans and rats, incubation with lovastatin was carried out. The inhibitory effects were observed by using chemical inhibitor specific to the CYP3A in humans. Results The enzyme kinetics in liver microsomes of minipigs were more similar to humans than rats. The metabolism of lovastatin in three various genera was significantly inhibited by ketoconazole. Conclusion Compared with rats, Bama miniature pigs are more suitable for the pharmacological studies related to CYP3A.
出处
《中国比较医学杂志》
CAS
2007年第6期329-332,337,共5页
Chinese Journal of Comparative Medicine
基金
国家"十五"科技攻关计划重点项目资助课题(2004BA717B-3)
