A dose-finding study of duloxetine based on serotonin transporter occupancy
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- Takano, A., Suzuki, K., Kosaka, J. et al. Psychopharmacology (2006) 185: 395. doi:10.1007/s00213-005-0304-0
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Positron emission tomography (PET) has been utilized for determining the dosage of antipsychotic drugs. To evaluate the dosage of antidepressants such as selective serotonin reuptake inhibitors, serotonin transporter occupancy (5-HTT) is also a useful index.
We investigated the degree of 5-HTT occupancy with different doses of the antidepressant duloxetine and the time-course of 5-HTT occupancy using PET.
PET scans with [11C]DASB were performed before and after a single administration of duloxetine (5–60 mg), and three consecutive scans were performed after a single dose or repeated doses of 60 mg of duloxetine.
5-HTT occupancies by duloxetine were increased by 35.3 to 86.5% with dose and plasma concentration increments. The ED50 value of 5-HTT occupancy was 7.9 mg for dose and 3.7 ng/ml for plasma concentration. In the time-course of 5-HTT occupancy, mean occupancies were 81.8% at 6 h, 71.9% at 25 h, and 44.9% at 53 h after a single administration, and 84.3% at 6 h, 71.9% at 49 h, and 47.1% at 78 h after repeated administrations.
Based on 5-HTT occupancy, 40 mg and more of duloxetine was needed to attain 80% occupancy, and 60 mg of duloxetine could maintain a high level of 5-HTT occupancy with a once-a-day administration schedule.