Henstra Marieke, Wong Liza, Chahbouni Abdel, Swart Noortje, Allaart Cor, Sombogaard Ferdi
a Department of Internal Medicine - Geriatrics , Academic Medical Center , Amsterdam , Netherlands.
b Department of Internal Medicine , VU University Medical Center , Amsterdam , Netherlands.
Clin Toxicol (Phila). 2017 Jul;55(6):600-602. doi: 10.1080/15563650.2017.1287372. Epub 2017 Feb 9.
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 k/k 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.
伊博格碱是一种被评估用于治疗药物依赖但未获批准的抗成瘾药物。已有报告称其使用会继发心源性猝死。我们描述了一名患者体内伊博格碱和去甲伊博格碱的临床效应及毒代动力学。为此，我们开发了一种液相色谱-串联质谱法来测定伊博格碱和去甲伊博格碱的血浆浓度。我们采用了具有一级吸收的二室模型。
伊博格碱的最高浓度为1.45毫克/升。我们的患者出现了明显延长的QTc间期，最长达647毫秒，还出现了多种心律失常（即房性心动过速、室性心动过速和尖端扭转型室速）。QTc延长一直持续到摄入后12天，此时伊博格碱血浆水平已很低，这表明在伊博格碱从血浆中清除很久之后，去甲伊博格碱的浓度仍具有临床相关性。去甲伊博格碱的k/k比值为21.5，伊博格碱为4.28，这表明与伊博格碱相比，去甲伊博格碱从外周室向中央室的分布较少。
我们证明了代谢产物浓度与作用持续时间之间存在线性关系，而非与母体伊博格碱。因此，在（长期）摄入伊博格碱后，临床医生应警惕其代谢产物引起的长期效应。
