Quetiapine extended-release versus immediate-release formulation: a positron emission tomography study

Area of Science:

• Neuroscience
• Pharmacology
• Radiochemistry

Background:

• Immediate-release (IR) quetiapine requires twice-daily dosing due to rapid plasma level and dopamine D(2) receptor occupancy fluctuations.
• An extended-release (XR) quetiapine formulation is under development for once-daily administration.
• Understanding central D(2) receptor binding is crucial for evaluating antipsychotic efficacy and dosing regimens.

Purpose of the Study:

• To compare the central dopamine D(2) receptor binding potential between IR and XR quetiapine formulations.
• To assess the pharmacokinetic and pharmacodynamic profiles of quetiapine XR for once-daily dosing efficacy.
• To provide data for determining equivalent doses and switching strategies between quetiapine formulations.

Main Methods:

• An open-label, crossover positron emission tomography (PET) study utilizing [(11)C]-raclopride.
• Comparison of central D(2) receptor binding potential at peak and trough plasma levels.
• Evaluation of equivalent daily doses (300, 600, 800 mg) of IR and XR quetiapine in 12 subjects.

Main Results:

• Mean plasma levels did not significantly differ between IR and XR formulations at trough and peak.
• Mean D(2) receptor occupancy at peak was significantly higher than at trough for most dose groups, with no significant difference between formulations.
• Trough plasma levels were significantly lower than peak levels for most groups, except for IR 300 and 800 mg.

Conclusions:

• Once-daily dosing of quetiapine XR provides peak and trough plasma levels comparable to twice-daily IR quetiapine.
• Central D(2) receptor occupancy profiles are similar between quetiapine IR and XR formulations with equivalent daily doses.
• Findings support the potential for once-daily dosing of quetiapine XR and inform dose equivalence and switching strategies.