- Cytochrome P450 enzyme substrate: Possibly CYP3A4
- Action to be taken: Monitor side effects, possible benefit
- Rationale: Mitoxantrone has shown to potentially induce cardiotoxicity. Study by Roseate et al, has shown that mitoxantrone cardiotoxic effects can be substantially decreased through inhibition of CYP450 enzymes. Invitro studies have shown that marijuana has an inhibitory effect on CYP3A4 enzyme. Metyrapone (CYP3A4 inhibitor) was shown to significantly decrease the cytotoxicity observed with the same concentration of Mitoxantrone in the absence of metyrapone. Therefore co- administration of marijuana with mitoxantrone may contribute to reduced cardiotoxicity associated with the drug.
- Furge, L. L. and Guengerich, F. P. (2006), Cytochrome P450 enzymes in drug metabolism and chemical toxicology: An introduction. Biochem. Mol. Biol. Educ., 34: 66–74. doi:10.1002/bmb.2006.49403402066
- Rossato L, Costa V, Remião F, et al. The metabolic profile of mitoxantrone and its relation with mitoxantrone-induced cardiotoxicity. Archives Of Toxicology [serial online]. October 2013;87(10):1809-1820. Available from: Environment Complete, Ipswich, MA. Accessed September 5, 2017.
- Watanabe K, Yamaori S, Funahashi T, et al. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci. 2007;80:1415-1419.
- Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014;46:86-95.