TY - JOUR
T1 - Population pharmacokinetic analysis for simultaneous determination of Bmax and KD In Vivo by positron emission tomography
AU - Liefaard, Lia C.
AU - Ploeger, Bart A.
AU - Molthoff, Carla F.M.
AU - Boellaard, Ronald
AU - Lammertsma, Adriaan A.
AU - Danhof, Meindert
AU - Voskuyl, Rob A.
PY - 2005/11/1
Y1 - 2005/11/1
N2 - 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.
AB - 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.
KW - Epilepsy
KW - Flumazenil
KW - GABA-receptor complex
KW - Population pharmacokinetic/pharmacodynamic modelling
KW - Positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=33644856838&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s11307-005-0022-3
DO - https://doi.org/10.1007/s11307-005-0022-3
M3 - Article
C2 - 16328648
SN - 1536-1632
VL - 7
SP - 411
EP - 421
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 6
ER -