INVESTIGATION INTO PHARMACOKINETIC PROPERTIES OF ACTIVE ALKALOID IBOGAINE AND ITS METABOLITE NORIBOGAINE

The interest in alkaloid ibogaine found in African plant Tabernanthe iboga Baill. has been persisting for several decades. Behavioral, neuroendocrine and neurochemical effects of ibogaine and its active metabolite - noribogaine - were examined, however there are limited pharmacokinetic data in literature and existing data is conflicting. We determined pharmacokinetic parameters of ibogaine and noribogaine not only in plasma, but in organs (heart, liver, spleen. brain, kidney and muscle) of mice after ibogaine and noribogaine intragastrical administration too. because there are no pharmacokinetic studies of internal organs. Circulating plasma levels of ibogaine and noribogaine peaked immediately at 30 min after ibogaine administration, whereas level of noribogaine after noribogaine administration increased slowly to plateau at 4 h. Shorter half-life (T-1/2) and smaller volume of distribution (Vd) of ibogaine show the faster elimination from plasma, compared with noribogaine. Largest Vd value in plasma calculated for noribogaine after noribogaine administration. Our results demonstrate that noribogaine reaches higher concentration in brain after ibogaine intragastrical administration. Higher concentration and total systemic exposure (AUC(tot)) of noribogaine in brain could be more efficacious alternative to ibogaine as a medication for the treatment of various types of addiction. High values of AUC(tot) in heart samples may determine the long elimination from this organ and can lead to cardiovascular abnormalities. Our findings also raise the hypothesis that ibogaine is metabolized not only in the liver, but also in kidney and brain too.