Sertraline, a recently introduced SSRI, is used in the treatment of depression and can be associated with various degrees of insomnia. The use of a short-acting hypnotic, such as zolpidem, could have significant clinical benefits in patients suffering from insomnia.This single-center, open, fixed-treatment-sequence study was conducted in 27 healthy female volunteers (mean age 30.1 yrs) with the objective to evaluate potential PK and PD interactions of five consecutive doses of nighttime zolpidem 10 mg (Z) together with sertraline 50 mg (S) as a single morning dose 13 days of S alone. PK and PD parameters were assessed after a single dose of Z (Day 2), after two weeks of S alone (Days 12-14), and during 5 days of co-administration of Z and S (Days 15-19).Steady-state plasma concentrations of S and its metabolite N-desmethylsertraline were not achieved after 14 days of treatment with S. Compared to PK results obtained after a single dose of Z, the mean C m a x of Z was significantly increased (+43%) and the mean T m a x was significantly decreased (-54%: 1.9 hrs vs 0.9 hrs) when Z was co-administered for 5 consecutive doses with S. The bioavailability of Z was not affected by coadministration with S. The presence of Z resulted in changes of PK parameters of S: a decrease in mean AUC (-6%) of S and an increase of the mean C m a x of the metabolite of S (+13%). The bioavailability of S was not modified by the presence of Z. Nine hours after Z, PD tests (DSST and others) were unchanged during the co-administration of Z and S compared to after single-dose treatment of Z.The overall incidence of adverse events (AE) was 7%, 32%, and 27% during the Z, S, and Z plus S dosing periods, respectively. These incidence rates cannot be compared since the lengths of dosing periods were not equal. No unexpected or serious AE occurred.While there was no significant change in the overall AUC of Z in presence of S, across the different dosing periods of this study, the higher C m a x and shorter T m a x suggests a shift in the AUC after multiple doses of Z in presence of S, with possible clinical impact on the onset of action of Z. The changes in the metabolism of S were relatively minor, but the dose of S (50 mg) is at the lower end of the therapeutic spectrum of S. Together with the absence of any PD interactions or changes in adverse events and their incidence, the co-administration of Z 10 mg and S 50 mg appears to be safe, though the continuous use of a higher dose drug regimen would have to be monitored.