大麻二酚对小鼠和人微粒体中环孢素和四氢大麻酚代谢的抑制作用。

Inhibition of cyclosporine and tetrahydrocannabinol metabolism by cannabidiol in mouse and human microsomes.

Jaeger W, Benet L Z, Bornheim L M

Department of Pharmacy, University of California, San Francisco 94143-0446, USA.

Xenobiotica. 1996 Mar;26(3):275-84. doi: 10.3109/00498259609046707.

Abstract

The in vitro and in vivo effects of cannabidiol on mouse and human liver microsomal metabolism of the immunosuppressive drug cyclosporine and the psychoactive compound tetrahydrocannabinol have been examined. 2. Preincubation of mouse or human liver microsomes with cannabidiol decreased the formation of all detectable cyclosporine metabolites by 73-89%. 3. In vivo cannabidiol treatment of mouse similarly decreased the formation of all detectable cyclosporine metabolites by 60-86%. 4. Preincubation of human liver microsomes with cannabidiol selectively decreased the formation of tetrahydrocannabinol metabolites catalyzed by cytochrome P4503A by 60% but had no effect on P4502C9-catalyzed metabolites. 5. Cannabidiol has the potential to clinically affect cyclosporine metabolism which may result in increased cyclosporine blood levels and an increase in its toxic side effects, and likewise may also affect tetrahydrocannabinol and its metabolite levels in man.

摘要

已经研究了大麻二酚对免疫抑制药物环孢素以及精神活性化合物四氢大麻酚在小鼠和人肝脏微粒体代谢中的体外和体内作用。2. 用大麻二酚预孵育小鼠或人肝脏微粒体，可使所有可检测到的环孢素代谢物的生成减少73 - 89%。3. 对小鼠进行体内大麻二酚治疗同样使所有可检测到的环孢素代谢物的生成减少60 - 86%。4. 用大麻二酚预孵育人肝脏微粒体可使细胞色素P4503A催化的四氢大麻酚代谢物的生成选择性减少60%，但对P4502C9催化的代谢物没有影响。5. 大麻二酚有可能在临床上影响环孢素的代谢，这可能导致环孢素血药浓度升高及其毒副作用增加，同样也可能影响人体中四氢大麻酚及其代谢物的水平。