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Methods and Findings
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Methods Find Exp Clin Pharmacol 2000, 22(2): 77
ISSN 0379-0355
Copyright 2000 Clarivate Analytics
CCC: 0379-0355
DOI: 10.1358/mf.2000.22.2.796066
 
 
Pharmacokinetic characterization of the indole alkaloid ibogaine in rats
Hough, L.B., Bagal, A.A., Glick, S.D.
 
 
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.


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