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Pablo J, Tyndale R, Obach S, Hearn WL, Mash DC. 
“Pharmacokinetic Disposition of Ibogaine after Oral Administration to Human Subjects”. 
College on Problems of Drug Dependence (CPDD). 1998 Jun.
Ibogaine, a drug used to treat opiate and cocaine dependence undergoes significant first-pass metabolism after oral dosing to O-desmethyl ibogaine (noribogaine). The metabolite appears to have increased therapeutic activity compared to the parent drug. Blood concentration-time effect profiles of ibogaine and noribogaine were obtained for individual subjects. The results demonstrated a multimodal frequency distribution of the logarithm of the subjects' (N=27) parent to metabolite ratios (ibogaine AUC / noribogaine AUC) derived from analysis of samples taken between zero and 24 hours post oral ibogaine. These distributions suggest the existence of three groups: poor metabolizers, intermediate metabolizers, or extensive metabolizers. In vitro studies have identified two cytochrome P-450 (CYP) isozymes involved in ibogaine metabolism: CYP2D6 and CYP3A4. The results demonstrate that the majority of ibogaine biotransformation proceeds via CYP2D6, including the o-demethylation of ibogaine to noribogaine. The results of CYP2D6 genotyping assays of these subjects demonstrated the existence of three groups (wt/wt, wt/null allele, and null allele/null allele). Taken together, these data suggest that the individual variability in the conversion of ibogaine to noribogaine may be due to pharmacogenetic polymorphism of CYP2D6, and the resulting differences in the levels of metabolite between individuals may be determinent in the resulting efficacy of treatment. Supported by the Addiction Research Fund.
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