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Doxepin is extensively metabolized by the liver via oxidation and N-demethylation. Its metabolism is highly stereoselective. Based on in vitro research, the major enzymes involved in the metabolism of doxepin are the cytochrome P450 enzymes CYP2D6 and CYP2C19, with CYP1A2, CYP2C9, and CYP3A4 also involved to a lesser extent. The major active metabolite of doxepin, nordoxepin, is formed mainly by CYP2C19 (> 50% contribution), while CYP1A2 and CYP2C9 are involved to a lesser extent, and CYP2D6 and CYP3A4 are not involved. Both doxepin and nordoxepin are hydroxylated mainly by CYP2D6, and both doxepin and nordoxepin are also transformed into glucuronide conjugates. The elimination half-life of doxepin is about 15â18 hours, whereas that of nordoxepin is around 28â31 hours. Up to 10% of Caucasian individuals show substantially reduced metabolism of doxepin that can result in up to 8-fold elevated plasma concentrations of the drug compared to normal.
Galantamine is produced from natural resources and a patented total synthesis process. Many other synthetic methods exist but have not been implemented on an industrial scale.
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