Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers.
Journal of clinical pharmacology June 1, 2015 Paul Glue, Helen Winter, Kira Garbe et al. 39 citations
Conversion of ibogaine to its active metabolite noribogaine is primarily mediated by the CYP2D6 enzyme. In a study of 21 healthy subjects given a single 20 mg oral dose of ibogaine after 6 days of pretreatment with either placebo or the CYP2D6 inhibitor paroxetine, those pretreated with paroxetine showed rapid absorption of ibogaine, with detectable levels lasting up to 72 hours and an elimination half-life of 10.2 hours. Noribogaine exposure was similar between groups, but the active moiety (ibogaine plus noribogaine) exposure was about 2-fold higher in paroxetine-pretreated subjects. CYP2D6 phenotype correlated strongly with ibogaine AUC and Cmax. The findings suggest genotyping patients before ibogaine treatment and halving the dose in CYP2D6 poor metabolizers to ensure safety.