The elimination half-life of donepezil is approximately 70 hours. Donepezil is well absorbed and reaches peak plasma concentrations in 3 to 4 hours. Donepezil is extensively metabolized to four major metabolites, two of which are known to be active, and a number of minor metabolites. Donepezil, metabolized by the CYP450 isoenzymes 2D6 and 3A4, undergoes glucuronidation. A small portion of donepezil is excreted in the urine intact.

In vitro studies show that ketoconazole and quinidine inhibit the metabolism of donepezil. A study was conducted examining the effect of coadministration of donepezil and ketoconazole in vivo. The ketoconazole increased the concentrations of donepezil, probably due to the inhibition of donepezil metabolism through CYP3A4. However, due to the small magnitude of concentration changes, dosage adjustment should not be necessary in clinical practice. Recently, two cases of moderately severe side effects were reported when donepezil was taken with paroxetine, suggesting possible interactions between donepezil and selective serotonin reuptake inhibitors as a result of CYP450 inhibition.

Rivastigmine is rapidly absorbed after oral administration (time to maximal plasma concentration ranges from 0.8 to 1.2 hours). The elimination half-life of rivastigmine is approximately 1 hour.

Rivastigmine is rapidly and extensively metabolized to produce the decarbamylated metabolite. Rivastigmine shows only weak binding to CYP450 isoenzymes in vitro. Renal elimination of the drug’s metabolite is rapid and essentially complete after 24 hours. No significant drug-drug interactions have been observed with 22 drug classes. Because rivastigmine demonstrates low protein binding (approximately 40%), no displacement of other drugs is expected.

It is unknown whether there are any drug interactions with galantamine.

The elimination half-life of galantamine is approximately 6 hours. Galantamine is both excreted unchanged and metabolized by the CYP450 isoenzyme 2D6 and 3A4. It has at least one active metabolite.