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 01, 2015
Source: PubMed
Summary
The body's processing of ibogaine is profoundly influenced by individual genetic differences. Research explored how the CYP2D6 enzyme affects the pharmacokinetics and pharmacodynamics of ibogaine, specifically its conversion to noribogaine. Healthy volunteers received a single ibogaine dose; some were pretreated with paroxetine to inhibit cyp2d6. Findings showed ibogaine was safely administered and rapidly converted to noribogaine. Inhibiting cyp2d6 doubled exposure to the active compounds, yet noribogaine levels remained similar. This highlights the importance of understanding cyp2d6 activity for optimizing ibogaine safety and effectiveness.
Abstract
Conversion of ibogaine to its active metabolite noribogaine appears to be mediated primarily by CYP2D6. We compared 168 hours pharmacokinetic profiles of both analytes after a single oral 20 mg dose of ibogaine in 21 healthy subjects who had been pretreated for 6 days with placebo or the CYP2D6 inhibitor paroxetine. In placebo-pretreated subjects, ibogaine was rapidly converted to noribogaine. Median peak noribogaine concentrations occurred at 4 hours. Compared with placebo-pretreated subjects, paroxetine-pretreated subjects had rapid (Tmax = 1.5 hours) and substantial absorption of ibogaine, with detectable levels out to 72 hours, and an elimination half-life of 10.2 hours. In this group, ibogaine was also rapidly converted to noribogaine with a median Tmax of 3 hours. Extent of noribogaine exposure was similar in both groups. CYP2D6 phenotype was robustly correlated with ibogaine AUC0-t (r = 0.82) and Cmax (r = 0.77). Active moiety (ibogaine plus noribogaine) exposure was ∼2-fold higher in paroxetine-pretreated subjects. Single 20 mg ibogaine doses were safe and well tolerated in all subjects. The doubling of exposure to active moiety in subjects with reduced CYP2D6 activity suggests it may be prudent to genotype patients awaiting ibogaine treatment, and to at least halve the intended dose of ibogaine in CYP2D6 poor metabolizers.