Pharmacokinetic characterization of the indole alkaloid ibogaine in rats.
L B Hough, A A Bagal, S D Glick
Methods and findings in experimental and clinical pharmacology March 1, 2000 DOI: 10.1358/mf.2000.22.2.796066 via PubMed
Summary
AI-generated from the abstractAfter a 20 mg/kg intravenous infusion in rats, ibogaine levels in plasma declined rapidly in a two-phase pattern, with an initial half-life of 7.3 minutes and a terminal half-life of 3.3 hours. Drug clearance was 5.9 L/h. Three hours after infusion, ibogaine concentrations in brain, liver, and kidney were 143–170 ng/g, but in adipose tissue the concentration was much higher at 3,328 ng/g. This sequestration in fat likely causes the drug to persist in the body longer than the terminal half-life suggests. The initial rapid disappearance from plasma may result from metabolic demethylation and redistribution to tissues.
Study at a glance
| Characteristics | Observational pharmacokinetic study Peer reviewed |
|---|---|
| Sample size | 7 |
| Population | Rats |
| Intervention | ibogaine |
| Dose | 20 mg/kg |
| Duration | Up to 3 h following i.v. infusion |
| Topics | Ibogaine |
| Keywords | Alkaloid Compound Pharmacokinetics Body processes |
| Citations | 7 |
| Key finding | Ibogaine accumulates in adipose tissue at much higher concentrations than in other tissues, suggesting a prolonged presence in the body that may be underestimated by the measured terminal half-life. |
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.