Population pharmacokinetic analysis for simultaneous determination of Bmax and KD In Vivo by positron emission tomography

Lia C. Liefaard, Bart A. Ploeger, Carla F.M. Molthoff, Ronald Boellaard, Adriaan A. Lammertsma, Meindert Danhof, Rob A. Voskuyl

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24 Citations (Scopus)


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 Bmax and KD. 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 Bmax 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 Bmax and KD for a group of animals using single injection PET experiments per animal.

Original languageEnglish
Pages (from-to)411-421
Number of pages11
JournalMolecular Imaging and Biology
Issue number6
Publication statusPublished - 1 Nov 2005


  • Epilepsy
  • Flumazenil
  • GABA-receptor complex
  • Population pharmacokinetic/pharmacodynamic modelling
  • Positron emission tomography

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