Quetiapine extended-release versus immediate-release formulation: a positron emission tomography study.
OBJECTIVE
The pharmacokinetic and pharmacodynamic profile of the immediate-release (IR) formulation of quetiapine is characterized by a rapid peak in plasma level and striatal dopamine D(2) receptor occupancy, followed by a rapid decrease to baseline levels, necessitating the use of twice-daily dosing. An extended-release (XR) formulation of quetiapine is currently being developed to achieve similar efficacy using a once-daily dosing regimen. We compared the central D(2) receptor binding between the IR and XR formulations.


METHODS
In this open-label, crossover positron emission tomography study using [(11)C]-raclopride, we compared the central D(2) receptor binding potential at expected peak and trough plasma levels using equivalent daily doses of the IR and XR formulations (300, 600, and 800 mg/day) in 12 subjects. Data were collected from April 2002 to May 2003.


RESULTS
The mean plasma level of quetiapine at trough was significantly lower than that at peak for all dose groups of both formulations except for IR 300 and 800 mg (all p values < .05), while the mean plasma level did not differ significantly between formulations at trough and peak. The mean occupancy at peak was significantly higher than that at trough for all dose groups other than IR 800 mg/day (all p values < .05) and did not differ significantly between formulations at trough and peak.


CONCLUSIONS
Once-daily dosing of the XR formulation gives peak and trough plasma levels and central D(2) receptor occupancy comparable to twice-daily dosing of the IR formulation. These data should be considered while determining equivalent doses, as well as switching strategies.
Mamo
David C
DC
Centre for Addiction and Mental Health, PET Centre, Toronto, Ontario, Canada.
Uchida
Hiroyuki
H
Vitcu
Irina
I
Barsoum
Penny
P
Gendron
Alain
A
Goldstein
Jeffrey
J
Kapur
Shitij
S
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D039721:Diagnostic and Statistical Manual of Mental Disorders; D003987:Dibenzothiazepines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D000069348:Quetiapine Fumarate; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D003987:Dibenzothiazepines; D017448:Receptors, Dopamine D2; D000069348:Quetiapine Fumarate