Pharmacokinetics Oral bioavailability of<unk>  was shown to be very high, up to 100%. Its bioavailability was tested by computing the drug's delivery rate across the rat's blood brain barrier. The drug concentration, reached in the brain, is 10-fold higher than plasma levels, verifying<unk>  as a brain-permeable AChE inhibitor. Relative to its short plasma half life of 8 to 12 minutes,<unk>  exhibits a long duration of action with the half-life of 8.25 hours in which the hindering effect on AChE is time-dependently faded. With the administration of<unk> , 70% or higher AChE inhibitory action in the blood was observed in preclinical studies and with systemic<unk>  administration, the extracellular ACh level in the striatum increased up to three times. Through PET studies and microdialysis, the compound's brain permeability was able to be further elucidated. Enantiomer (posiphen) (-)-Phenserine, generally referred to<unk> , acts as an active enantiomer for the inhibition of acetylcholinesterase (AChE) while posiphen, its alternative enantiomer, was comparably demonstrated as a poor AChE inhibitor. In the history of posiphen research, several companies were interactively involved. In 2005, an Investigational New Drug (IND) application of posiphen was filed with FDA by TorreyPines Therapeutics while its phase I trial on animal models had been implemented by Axonyx. Axonyx and TorreyPines Therapeutics officially signed for their merger agreement in 2006 and licensed the drug to QR Pharma in 2008. The clinical trials of posiphen against Alzheimer's disease are still underway. Although the ongoing clinical trials yet have affirmed if posiphen can be pursued as a novel Alzheimer's disease's treatment, posiphen has demonstrated its potential by impeding neurodegenerative mechanisms. Posiphen performs in a noncholinergic manner, including but not limited to, the suppressing action on APP translation and β-secretase Activity. The β-secretase Activity is instigated by the accumulation of Aβ peptides which are augmented along with aging of the human brain. In clinical demonstrations with brain cell-lines, two contrasting forms showed the noncholinergic mechanism to an equal extent, with respect to their potency and efficacy. Posiphen is relatively well tolerated with the administration of doses, even higher than the maximally tolerable dose of (-)-phenserine. In vivo, the levels of APP protein in the cortex were reduced by posiphen with an ED50 (median Effective Dose). The β-secretase activity in the mouse brain also could be reduced with elevated doses of 35 and 50 mg/kg. Overall, the dose range from 10 mg to 160 mg of posiphen is well tolerated and generally adopted in clinical uses. With higher doses, supralinear increase of plasma levels was shown, indicating the saturable metabolism, which is a factor related to toxicity. Studies have shown that plasma levels of posiphen reducing brain Aβ levels are equal or greater in humans than mice. Once posiphen is exceedingly dosed over 160 mg, gastro-intestinal related symptoms including nausea and vomiting, were manifested. The drug additionally presents the rapid absorption rate, occurred within an hour or two. Pharmacokinetics of posiphen was overall kept linear. Interactions Currently, 282 drugs have been reported to make interactions with<unk> .
Phenserine
Nicotinamide
Glutamate 
Glutamine
Choline
Carnitine
Pyridinoline
Gamma-Amino-beta-hydroxybutyric acid