Concentration of Prozac can achieve relatively high levels. It becomes maximal in 6-8 hours after medicine intake. Plasma proteins, particularly albumin, highly bind Prozac.
Enzyme CYP2D6 of cytochrome P450 system helps to metabolize Prozac. Reaction of Prozac metabolism happens in the liver. There is wide range of genetic variability in the function of CYP2D6 that’s why the role of that enzyme in the metabolism of Prozac may be clinically essential.
The distinctive feature of Prozac and its active metabolite norfluoxetine from other antidepressant medications is their very slow excretion. Half –life of Prozac elimination can vary from 1-3 days after single dose to 4-6 day of after continuous use. Likewise, the half-life of norfluoxetine becomes longer (16 days) after long termed use. That fact can be explained due to that Prozac and norfluoxetine inhibit their own metabolism with time. That’s why drug and its active metabolite concentration in blood keeps on growing during the first weeks of therapy, and their steady concentration in the blood is achieved only after four weeks after treatment beginning. Moreover, the brain levels of Prozac and its metabolites have been increasing through at least the first five weeks of treatment. A patient receives the full benefits of the current dose for at least a month since its initiation. The average of achieving consistent response is about 29 days. Likewise, complete elimination of Prozac may take several weeks. The brain levels of Prozac run down only by 50% during the first week after the treatment had been discontinued, The blood level of norfluoxetine after 4 weeks the treatment discontinuation is about 80% of the level registered by the end of the first treatment week, and after 7 weeks the treatment had been discontinued it is still possible to detect norfluoxetine in the blood.
Prozac levels in brain increases very slowly during first 5 weeks of therapy. It is distinction feature of Prozac’s pharmacokinetics. That fact aggravates to find out the most optimal dose for continuous treatment. It was proved that one 60-mg dose of Prozac per week has similar effect as 20 mg/day for the continuation treatment of patients responding to 20 mg/day of Prozac. 5 mg/day Prozac was significantly superior to placebo and equivalent to 20 mg/day; while Prozac 80 mg/week had similar results as 60 mg/day Prozac or 150 mg/day amitriptyline. Increasing of dose to 60mg/day in patients who did not respond to 20mg/day therapy is not essentially different from results got in patients continuing the 20 mg/day treatment.
There is speculation based on the results of recent trials. It tries to explain the resistance to the SSRIs Paxil and Celexa. That hypothesis says that the genetic variation of P-glycoprotein (Pgp) transporter can induce resistance to abovementioned medications. Paxil and Celexa are Pgp substrates and Pgp carries them from the brain, while Prozac is not a substrate of that protein. That’s why replacement of Paxil and Celexa with Prozac can bring positive dynamics in patients who don’t respond on those drugs.