Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers.
Level 2 - randomized trial
Controlled clinical pharmacokinetic trial in healthy volunteers
PubMed 25651476 · doi:10.1002/jcph.471
What was done
Researchers measured the 168-hour pharmacokinetic profiles of ibogaine and its active metabolite noribogaine following a single 20 mg oral dose of ibogaine in 21 healthy subjects. Participants were pretreated for 6 days with either placebo or the CYP2D6 inhibitor paroxetine to determine the impact of CYP2D6 activity on drug metabolism and exposure.
What was found
In placebo-pretreated participants, ibogaine converted rapidly to noribogaine with median noribogaine peak concentrations at 4 hours. In paroxetine-pretreated participants, ibogaine displayed rapid absorption (Tmax = 1.5 hours), detectable levels up to 72 hours, an elimination half-life of 10.2 hours, and median noribogaine Tmax at 3 hours. Noribogaine exposure was similar between groups, but CYP2D6 phenotype strongly correlated with ibogaine AUC0-t (r = 0.82) and Cmax (r = 0.77). Total active moiety exposure (ibogaine plus noribogaine) was approximately twofold higher in the paroxetine group. Doses were safe and well-tolerated.
Why it matters
Because CYP2D6 inhibition doubles overall active drug exposure, patients receiving ibogaine may benefit from CYP2D6 genotyping or substantial dose reductions if they are poor metabolizers, reducing the risk of toxicity.
Limits
The study tested only a single low dose (20 mg, far below therapeutic or recreational doses) in a small cohort of 21 healthy volunteers, pharmacodynamic parameters were not detailed with numerical endpoints in the abstract, and whether assignment was randomized or crossover was not specified in the abstract.
Cited by
- supports Noribogaine exhibits a cardiac risk profile similar to ibogaine, and ibogaine is metabolized into noribogaine via the CYP2D6 enzyme over roughly 8 to 12 hours.