Rat: A comparison is shown of plasma, brain and CSF levels of Posiphen and metabolites undertaken under steady-state conditions, which was achieved by continuous administration of Posiphen 75 mg/kg/day for 10 days by osmotic mini pump. In rat plasma (ng/ml) and brain (ng/g wet weight), Posiphen proved to be the primary drug compound, with the two major metabolites, N1- and N8-norposiphen, comprising up to 39.1% of Posiphen in plasma and up to 22% of Posiphen in brain at the Cmax. The third metabolite, N1, N8-bisnorposiphen, reached 20.4% of Posiphen in plasma and 3.8% of Posiphen at Cmax in brain. Human: the pharmacokinetic parameters of Posiphen and metabolites are shown in plasma and CSF of MCI patients after 10 days of 4×60 mg/day repeat dose oral administration, male and female subjects combined. As expected from the rodent data, the two primary metabolites N1- and N8-norposiphen constitute approximately 20% of Posiphen at the Cmax, with the third metabolite N1, N8-bisnorposiphen being a minor component and reaching only 3% of Posiphen Cmax. The time-dependent pharmacokinetic profiles of Posiphen and metabolites are provided in figure 3.

↵* The ClogP value is an established measure of a compound's lipid versus water solubility, with a positive value associated with a preference for the lipid phase.

MCI, mild cognitive impairment.