Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers
OrthoEvidence Journal (OE Journal) - ACE Report
OE Journal. 2022;10(14):12 J Clin Pharmacol. 2015 23-Feb;():. 10.1002/jcph.471What this means for my practice?
Single doses of ibogaine were safe and well-tolerated. The reduced CYP2D6 activity in paroxetine-treated subjects provided a doubling in exposure to active moiety. This result indicates the importance of characterizing the CYP2D6 genotype/phenotype for patients awaiting ibogaine treatment and to adjust ibogaine doses for CYP2D6 poor metabolizers. Limitations include the small sample size and the use of all males. Additionally, other cytochromes may have been involved in the pharmacokinetics of ibogaine and were not genotyped.
Study Summary
Twenty-one healthy subjects underwent a randomized study to examine the influence of cytochrome P450 (CYP) 2D6 on the pharmacokinetics of a single dose of ibogaine (20 mg). Subjects were pretreated either with placebo or the CYP2D6 inhibitor paroxetine. Ibogaine was rapidly converted to noribogaine in the placebo subjects. The paroxetine subjects had ~2-fold higher exposure to active moiety (ibogaine plus noribogaine) compared to placebo subjects.
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