Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaine.

A single patient who took ibogaine, an unapproved anti-addictive agent, developed a severely prolonged QTc interval of 647 milliseconds and multiple cardiac arrhythmias, including atrial tachycardia, ventricular tachycardia, and Torsades de Pointes. The QTc prolongation persisted for 12 days after ingestion, even after ibogaine plasma levels had become low. A newly developed LC-MS/MS method measured ibogaine and noribogaine concentrations, revealing that noribogaine, the metabolite, remained at clinically relevant levels long after ibogaine cleared. A linear relationship was found between noribogaine concentration and the prolonged cardiac effects, implicating the metabolite rather than the parent drug in the extended duration of cardiac arrhythmia risk.

Study at a glance

Abstract

Ibogaine is an agent that has been evaluated as an unapproved anti-addictive agent for the management of drug dependence. Sudden cardiac death has been described to occur secondary to its use. We describe the clinical effects and toxicokinetics of ibogaine and noribogaine in a single patient. For this purpose, we developed a LC-MS/MS-method to measure ibogaine and noribogaine plasma-concentrations. We used two compartments with first order absorption. The maximum concentration of ibogaine was 1.45 mg/L. Our patient developed markedly prolonged QTc interval of 647ms maximum, several multiple cardiac arrhythmias (i.e., atrial tachycardia and ventricular tachycardia and Torsades des Pointes). QTc-prolongation remained present until 12 days after ingestion, several days after ibogaine plasma-levels were low, implicating clinically relevant noribogaine concentrations long after ibogaine had been cleared from the plasma. The ratio k12/k21 for noribogaine was 21.5 and 4.28 for ibogaine, implicating a lower distribution of noribogaine from the peripheral compartment into the central compartment compared to ibogaine. We demonstrated a linear relationship between the concentration of the metabolite and long duration of action, rather than with parent ibogaine. Therefore, after (prolonged) ibogaine ingestion, clinicians should beware of long-term effects due to its metabolite.