Abstract
Duloxetine is a new antidepressant candidate drug with inhibitory effects on norepinephrine and serotonin (5-HT) uptake. In the present study, simultaneous monitoring of the inhibition of 5-HT uptake by platelets and plasma drug concentrations was carried out in healthy volunteers during and after administration of 20 mg of duloxetine once daily for 1 week. Inhibition by duloxetine of 5-HT uptake by platelets and the appearance of the drug in plasma occurred simultaneously, and a strong inhibition greater than 80% to 90% was maintained during the experimental period. Until 2 days after the final administration, the observed values for 5-HT uptake inhibition rate were in good agreement with those simulated from total, but not final, plasma concentrations of duloxetine ( r = .9846). Moreover, on the fourth day after the final administration, the observed values were even higher than the simulated ones (observed mean value, 40.5 ± 14.6; simulated value, 13.3). These results show that uptake of 5-HT is inhibited strongly and for a long period in the subjects taking duloxetine.
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