Loading...
Fluoxetine is known as both a substrate and inhibitor of cytochrome P (CYP) 450 2D6, leading to attempts to predict its actions in patients with different 2D6 genotypes and its interactions with other 2D6 substrates. Researchers examined whether knowing about this enzyme is sufficient to predict clinical interactions.
In vitro, both fluoxetine and its major active metabolite, norfluoxetine, were strong inhibitors of 2D6, 2C19, and 3A4. In vivo, 12 to 14 days of fluoxetine administration in 10 normal subjects significantly reduced clearance of the 2D6 substrate dextromethorphan and the 2C19 substrate omeprazole (but did not alter its elimination half-life). Clearance and half-life of the 3A4 substrate midazolam were unchanged, because fluoxet…