1995 Volume 10 Issue supplement Pages 142-145
Cytochrome P450 isozymes involvement in the metabolic activation of tetrahydrocannabinol (THC) have been investigated. CYP2C29 was a major isozyme responsible for 11-hydroxylation as well as 7α- and 8 α-hydroxylation of THC in the mouse liver. In rats, CYP2C11 and CYP2C6 were major isozymes involvement in the 11-hydroxylation of THC in the male and female rat liver, respectively. P450G-A belonging to CYP2B subfamily was a major isozyme for metabolizing THC in the guinea pig liver. In monkey liver, P450RM-A (CYP2A) and P450JM-D (CYP2C), and P45OJM-C (CYP2B) were responsible for the 11-hydroxylation and 3'-hydroxylation of TUC, respectively. the 11-hydroxylation of TUC In human liver was also catalyzed by P450 isozyme belonging to CYP2C, weheras 8 β-hydroxylation of Δ9-TIC and 7 α-hydroxylation of Δ8-THC were catalyzed by CYP3A. The present results indicate that CYP2C Is mainly responsible for the metabolic activation of 1HC in most of animals including humans, while CYP2A has some role in the metabolic activation of 1W in the monkey liver.
