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

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Citation

Caille F, Goutal S, Marie S, Auvity S, Cisternino S, Kuhnast B, Pottier G, Tournier N

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

Contrast Media Mol Imaging. 2018 May 8;2018:7310146. doi: 10.1155/2018/7310146. eCollection 2018.

PubMed ID
29853808 [ View in PubMed
]
Abstract

Positron emission tomography (PET) imaging using [(11)C]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 [(11)C]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 [(11)C]metoclopramide kinetics and metabolism in plasma (n=3) were measured using radio-HPLC analysis. [(11)C]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 [(11)C]metoclopramide kinetics in plasma, respectively. The pharmacologic dose of metoclopramide resulted in a approximately 2.2-fold increase in [(11)C]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). [(11)C]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.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
MetoclopramideP-glycoprotein 1ProteinHumans
Unknown
Substrate
Details