Pharmacokinetic characterization of the indole alkaloid ibogaine in rats.
Methods and findings in experimental and clinical pharmacology – March 01, 2000
Source: PubMed
Summary
A remarkable finding shows ibogaine, an alkaloid with potential anti-addictive properties, rapidly clears from the bloodstream yet significantly accumulates in fat tissue. To understand how the body processes this compound, scientists measured its levels in rats' plasma and various organs after intravenous infusion. They observed a swift redistribution from plasma, with levels declining rapidly then more slowly. Importantly, ibogaine concentrated far more in adipose tissue than in other organs. This strong accumulation suggests a prolonged presence in the body, profoundly impacting its overall duration.
Abstract
To investigate the pharmacokinetic properties of ibogaine, a putatively anti-addictive alkaloid, levels of this drug were quantified in plasma and tissues for up to 3 h following i.v. infusion in rats. Immediately following a 31-35 min infusion (20 mg/kg), mean plasma ibogaine levels were 373 ng/ml; these values declined rapidly thereafter in a biexponential manner. The plasma time course in 5 of 7 animals demonstrated an excellent fit to a two-compartment pharmacokinetic model, with alpha and beta half-lives of 7.3 min and 3.3 h, respectively. Drug clearance was estimated to be 5.9 l/h (n = 7). Ibogaine levels in brain, liver and kidney 3 h after the end of drug infusion were 143-170 ng/g, close to simulated values for the peripheral pharmacokinetic compartment. However, 3-h drug levels in adipose tissue were much higher (3,328 ng/g), implying the need for a more complex pharmacokinetic model. Mechanisms for the initial, rapid disappearance of plasma ibogaine are thought to include metabolic demethylation as well as redistribution to body stores. The sequestration of ibogaine by adipose tissue probably contributes to a protracted persistence of drug in the body. This persistence may be underestimated by the beta half-life reported in the present study.