PMID- 29967572
OWN - NLM
STAT- MEDLINE
DCOM- 20190710
LR  - 20240327
IS  - 1555-4317 (Electronic)
IS  - 1555-4309 (Print)
IS  - 1555-4309 (Linking)
VI  - 2018
DP  - 2018
TI  - Physiologically Based Pharmacokinetic Modelling with Dynamic PET Data to Study 
      the In Vivo Effects of Transporter Inhibition on Hepatobiliary Clearance in Mice.
PG  - 5849047
LID - 10.1155/2018/5849047 [doi]
LID - 5849047
AB  - Physiologically based pharmacokinetic modelling (PBPK) is a powerful tool to 
      predict in vivo pharmacokinetics based on physiological parameters and data from 
      in vivo studies and in vitro assays. In vivo PBPK modelling in laboratory animals 
      by noninvasive imaging could help to improve the in vivo-in vivo translation 
      towards human pharmacokinetics modelling. We evaluated the feasibility of PBPK 
      modelling with PET data from mice. We used data from two of our PET tracers under 
      development, [(11)C]AM7 and [(11)C]MT107. PET images suggested hepatobiliary 
      excretion which was reduced after cyclosporine administration. We fitted the 
      time-activity curves of blood, liver, gallbladder/intestine, kidney, and 
      peripheral tissue to a compartment model and compared the resulting 
      pharmacokinetic parameters under control conditions ([(11)C]AM7 n = 2; 
      [(11)C]MT107, n = 4) and after administration of cyclosporine ([(11)C]MT107, n = 
      4). The modelling revealed a significant reduction in [(11)C]MT107 hepatobiliary 
      clearance from 35.2 +/- 10.9 to 17.1 +/- 5.6 mul/min after cyclosporine 
      administration. The excretion profile of [(11)C]MT107 was shifted from 
      predominantly hepatobiliary (CL(H)/CL(R) = 3.8 +/- 3.0) to equal hepatobiliary and 
      renal clearance (CL(H)/CL(R) = 0.9 +/- 0.2). Our results show the potential of PBPK 
      modelling for characterizing the in vivo effects of transporter inhibition on 
      whole-body and organ-specific pharmacokinetics.
FAU - Taddio, Marco F
AU  - Taddio MF
AUID- ORCID: 0000-0003-2477-5575
AD  - Radiopharmaceutical Science and Biopharmacy, Institute of Pharmaceutical 
      Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, 
      Switzerland.
FAU - Mu, Linjing
AU  - Mu L
AD  - Department of Nuclear Medicine, University Hospital Zurich, Switzerland.
FAU - Keller, Claudia
AU  - Keller C
AD  - Radiopharmaceutical Science and Biopharmacy, Institute of Pharmaceutical 
      Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, 
      Switzerland.
FAU - Schibli, Roger
AU  - Schibli R
AUID- ORCID: 0000-0002-1537-3833
AD  - Radiopharmaceutical Science and Biopharmacy, Institute of Pharmaceutical 
      Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, 
      Switzerland.
FAU - Kramer, Stefanie D
AU  - Kramer SD
AUID- ORCID: 0000-0002-0426-4340
AD  - Radiopharmaceutical Science and Biopharmacy, Institute of Pharmaceutical 
      Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, 
      Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180603
PL  - England
TA  - Contrast Media Mol Imaging
JT  - Contrast media & molecular imaging
JID - 101286760
RN  - 0 (Carbon Radioisotopes)
RN  - 0 (Carrier Proteins)
RN  - 0 (Radiopharmaceuticals)
RN  - 83HN0GTJ6D (Cyclosporine)
SB  - IM
MH  - Animals
MH  - Carbon Radioisotopes
MH  - Carrier Proteins/antagonists & inhibitors
MH  - Cyclosporine/*pharmacology
MH  - Hepatobiliary Elimination/*drug effects
MH  - Humans
MH  - Metabolic Clearance Rate/*drug effects
MH  - Mice
MH  - Models, Theoretical
MH  - Pharmacokinetics
MH  - Positron-Emission Tomography/*methods
MH  - Radiopharmaceuticals
PMC - PMC6008768
EDAT- 2018/07/04 06:00
MHDA- 2019/07/11 06:00
PMCR- 2018/06/03
CRDT- 2018/07/04 06:00
PHST- 2018/01/30 00:00 [received]
PHST- 2018/02/20 00:00 [accepted]
PHST- 2018/07/04 06:00 [entrez]
PHST- 2018/07/04 06:00 [pubmed]
PHST- 2019/07/11 06:00 [medline]
PHST- 2018/06/03 00:00 [pmc-release]
AID - 10.1155/2018/5849047 [doi]
PST - epublish
SO  - Contrast Media Mol Imaging. 2018 Jun 3;2018:5849047. doi: 10.1155/2018/5849047. 
      eCollection 2018.