The oxidative activities of 7α- and 7β-hydroxy-Δ8- tetrahydrocannabinol (7α- and 7β-hydroxy-Δ8-THC) to 7-oxo-Δ8-THC in hepatic microsomes of mice were significantly increased by the treatment of mice with dexamethasone or phenobarbital. A cytochrome P450 enzyme, named P450MDX-B, was purified from hepatic microsomes of dexamethasone-treated mice, and its apparent molecular mass was estimated to be 51,000. The NH2- terminal amino acid sequence of P450MDX-B was the same as that of CYP3A11. The oxidative activities of 7α- and 7β-hydroxy-Δ8-THC were 2.55 and 4.92 nmol/min/nmol P450, respectively. The antibody against P450MDX-B almost completely inhibited the oxidative activities of 7α- and 7β-hydroxy-Δ8- THC in mice. These results indicate that P450MDX-B (CYP3A11) is a major enzyme responsible for the oxidation of 7α- and 7β-hydroxy-Δ8-THC to 7- oxo-Δ8-THC in mouse liver.
|Number of pages||3|
|Journal||Drug Metabolism and Disposition|
|Publication status||Published - Oct 1 1998|
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science