Positron Emission Tomography Imaging Reveals an Importance of Saturable Liver Uptake Transport for the Pharmacokinetics of Metoclopramide

Contrast Media & Molecular Imaging
Fabien CailléNicolas Tournier

Abstract

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 hepa...Continue Reading

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Citations

Jan 25, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Pierre BonnaventureCatherine M Pastor
Dec 20, 2019·EJNMMI Radiopharmacy and Chemistry·Verena PichlerWolfgang Wadsak
May 12, 2018·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Sylvain AuvityNicolas Tournier
Dec 7, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Viktoria ZoufalOliver Langer
Jan 12, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Nicolas TournierOliver Langer
Sep 10, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Louise BreuilNicolas Tournier

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