Positron Emission Tomography Imaging Reveals an Importance of Saturable Liver Uptake Transport for the Pharmacokinetics of Metoclopramide
Joint Authors
Cisternino, Salvatore
Caillé, Fabien
Goutal, Sébastien
Marie, Solène
Auvity, Sylvain
Kuhnast, Bertrand
Pottier, Géraldine
Tournier, Nicolas
Source
Contrast Media & Molecular Imaging
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-05-08
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Positron emission tomography (PET) imaging using [11C]metoclopramide, a P-glycoprotein (P-gp) substrate, was used to investigate the contribution of transport processes to metoclopramide liver clearance.
The liver kinetics obtained after injection of [11C]metoclopramide were measured using PET in rats (n=4‐5) in the absence (tracer dose) and the presence of a pharmacologic dose of metoclopramide (3 mg/kg), with or without P-gp inhibition using i.v.
tariquidar (8 mg/kg).
Corresponding [11C]metoclopramide kinetics and metabolism in plasma (n=3) were measured using radio-HPLC analysis.
[11C]metoclopramide exposure to the liver and plasma was described by the area under the time-activity curve (AUC) of the radioactivity kinetics in the liver and parent [11C]metoclopramide kinetics in plasma, respectively.
The pharmacologic dose of metoclopramide resulted in a ∼2.2-fold increase in [11C]metoclopramide AUCplasma, while P-gp inhibition did not.
AUCliver was lower using the pharmacologic dose (42.9 ± 13.8 SUV·min) compared with the tracer dose (210.0 ± 32.4 SUV·min).
P-gp inhibition enhanced the liver exposure in the pharmacologic condition only (81.0 ± 3.1 SUV·min).
[11C]metoclopramide PET imaging suggests an unpredicted role for hepatocyte uptake transporter(s) in controlling metoclopramide pharmacokinetics in addition to the known contribution of the metabolic enzymes and the P-gp.
American Psychological Association (APA)
Caillé, Fabien& Goutal, Sébastien& Marie, Solène& Auvity, Sylvain& Cisternino, Salvatore& Kuhnast, Bertrand…[et al.]. 2018. Positron Emission Tomography Imaging Reveals an Importance of Saturable Liver Uptake Transport for the Pharmacokinetics of Metoclopramide. Contrast Media & Molecular Imaging،Vol. 2018, no. 2018, pp.1-8.
https://search.emarefa.net/detail/BIM-1131525
Modern Language Association (MLA)
Caillé, Fabien…[et al.]. Positron Emission Tomography Imaging Reveals an Importance of Saturable Liver Uptake Transport for the Pharmacokinetics of Metoclopramide. Contrast Media & Molecular Imaging No. 2018 (2018), pp.1-8.
https://search.emarefa.net/detail/BIM-1131525
American Medical Association (AMA)
Caillé, Fabien& Goutal, Sébastien& Marie, Solène& Auvity, Sylvain& Cisternino, Salvatore& Kuhnast, Bertrand…[et al.]. Positron Emission Tomography Imaging Reveals an Importance of Saturable Liver Uptake Transport for the Pharmacokinetics of Metoclopramide. Contrast Media & Molecular Imaging. 2018. Vol. 2018, no. 2018, pp.1-8.
https://search.emarefa.net/detail/BIM-1131525
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1131525