Purpose
Changes in GABAA-receptor density and affinity play an important role in many forms of epilepsy. A novel approach, using positron emission tomography (PET) and [C-11]flumazenil ([C-11]FMZ), was developed for simultaneous estimation of GABAA-receptor properties, characterized by B max and K D.
Procedures
Following an injection of [C-11]FMZ (dose range: 1–2,000 μg) to 21 rats, concentration time curves of FMZ in brain (using PET) and blood (using HPLC-UV) were analyzed simultaneously using a population pharmacokinetic (PK) model, containing expressions to describe the time course of the plasma concentration (including distribution to the body), the brain distribution, and the specific binding within the brain.
Results
Application of this method in control rats resulted in estimates of B max and K D (14.5 ± 3.7 ng/ml and 4.68 ± 1.5 ng/ml, respectively).
Conclusions
The proposed population PK model allowed for simultaneous estimation of B max and K D for a group of animals using single injection PET experiments per animal.