In healthy subjects, pharmacokinetics were characterised using single oral and sublingual administrations of the β-carboline norharman. For this purpose, norharman levels in blood plasma were measured up to 90-105 min after both routes of administration. Dose proportionality of three different single oral doses of norharman (7, 65 and 110 μg/kg) administered as 0.52 and 5 mg capsules was evaluated at 8 time points. Peak levels were attained at 30 min after the oral load of norharman. Mean relative availabilities determined by the area under the curve (AUC) procedure were 14.3 and 98.0 nmol.min/l after oral dosing of 7 and 65 μg/kg, respectively. AUC values in women were 3-4 times higher than in men. Sublingual dosing of 6.5 and 13 μg/kg norharman encapsulated in 5 mg of cyclodextrins resulted in a much higher mean AUC and a more rapid absorption. Mean AUC after sublingual administration of 6.5 μg/kg was 929.8 nmol.min/kg and plasma levels were maximal 10-15 min after norharman was given. Moreover, apparently no sex difference was found using this way of application. Norharman disappeared from the plasma with half-lifes of 25-35 min, irrespective of the route of administration. Even at the highest measured norharman levels of 53 nmol/l plasma, no behavioral effects were observed. In addition, the subjects did neither report any effects nor any side-effects during the experiment. This is the first study in which the kinetics of ingested norharman have been measured in humans.

β-carboline, Norharman, Pharmacokinetics, Sublingual dosing,
Life Sciences
Erasmus MC: University Medical Center Rotterdam

Fekkes, D, Tuiten, A, Bom, I, & Pepplinkhuizen, L. (2001). Pharmacokinetics of the β-carboline norharman in man. Life Sciences, 69(18), 2113–2121. doi:10.1016/S0024-3205(01)01293-0