SIMULTANEOUS MONITORING OF INHIBITION OF SEROTONIN UPTAKE BY PLATELETS AND PLASMA DRUG CONCENTRATIONS FOLLOWING ADMINISTRATION OF DULOXETINE, A NEW ANTIDEPRESSANT CANDIDATE, TO HEALTHY-VOLUNTEERS

Duloxetine is a new antidepressant candidate drug with inhibitory effe cts on norepinephrine and serotonin (5-HT) uptake. In the present stud y, simultaneous monitoring of the inhibition of 5-HT uptake by platele ts and plasma drug concentrations was carried out in healthy volunteer s during and after administration of 20 mg of duloxetine once daily fo r 1 week. Inhibition by duloxetine of 5-HT uptake by platelets and the appearance of the drug in plasma occurred simultaneously, and a stron g inhibition greater than 80% to 90% was maintained during the experim ental period. Until 2 days after the final administration, the observe d values for 5-HT uptake inhibition rate were in good agreement with t hose simulated from total, but not final, plasma concentrations of dul oxetine (r = .9846). Moreover, on the fourth day after the final admin istration, the observed values mere even higher than the simulated one s (observed mean value, 40.5 +/- 14.6; simulated value, 13.3). These r esults show that uptake of 5-HT is inhibited strongly and for a long p eriod in the subjects taking duloxetine.