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Fluoxetine is well absorbed after oral intake, is highly protein bound, and has a large volume of distribution. The elimination half-life of fluoxetine is about 1 to 4 days, while that of its metabolite norfluoxetine ranges from 7 to 15 days. Fluoxetine has a nonlinear pharmacokinetic profile. Therefore, the drug should be used with caution in patients with a reduced metabolic capability (i.e. hepatic dysfunction). In contrast with its effect on the pharmacokinetics of other antidepressants, age does not affect fluoxetine pharmacokinetics. This finding together with the better tolerability profile of fluoxetine (compared with tricyclic antidepressants) makes this drug particularly suitable for use in elderly patients with depression. Furthermore, the pharmacokinetics of fluoxetine are not affected by either obesity or renal impairment. On the basis of results of plasma concentration-clinical response relationship studies, there appears to be a therapeutic window for fluoxetine. Concentrations of fluoxetine plus norfluoxetine above 500 micrograms/L appear to be associated with a poorer clinical response than lower concentrations. Fluoxetine interacts with some other drugs. Concomitant administration of fluoxetine increased the blood concentrations of antipsychotics or antidepressants. The interactions between fluoxetine and lithium, tryptophan and monoamine oxidase inhibitors, in particular, are potentially serious, and can lead to the 'serotonergic syndrome'. This is because of synergistic pharmacodynamic effects and the influence of fluoxetine on the bioavailability of these compounds.

Basing on the assumption that frontotemporal lobar degeneration (FTLD), schizophrenia and bipolar disorder (BPD) might share common aetiological mechanisms, we analyzed genetic variation in the FTLD risk gene progranulin (GRN) in a German population of patients with schizophrenia (n = 271) or BPD (n = 237) as compared with 574 age-, gender- and ethnicity-matched controls. Furthermore, we measured plasma progranulin levels in 26 German BPD patients as well as in 61 Italian BPD patients and 29 matched controls.A significantly decreased allelic frequency of the minor versus the wild-type allele was observed for rs2879096 (23.2 versus 34.2%, P<0.001, OR:0.63, 95%CI:0.49–0.80), rs4792938 (30.7 versus 39.7%, P = 0.005, OR: 0.70, 95%CI: 0.55–0.89) and rs5848 (30.3 versus 36.8, P = 0.007, OR: 0.71, 95%CI: 0.56–0.91). Mean±SEM progranulin plasma levels were significantly decreased in BPD patients, either Germans or Italians, as compared with controls (89.69±3.97 and 116.14±5.80 ng/ml, respectively, versus 180.81±18.39 ng/ml P<0.001) and were not correlated with age.In conclusion, GRN variability decreases the risk to develop BPD and schizophrenia, and progranulin plasma levels are significantly lower in BPD patients than in controls. Nevertheless, a larger replication analysis would be needed to confirm these preliminary results.

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