Linnik, Inna, Rayner, Peter John orcid.org/0000-0002-6577-4117, Stow, Ruth et al. (2 more authors) (2019) Pharmacokinetics of the SABRE agent 4,6-d2-Nicotinamide and also Nicotinamide in rats following oral and intravenous administration. European journal of pharmaceutical sciences. EJPS-D-19-00374R1. pp. 32-37. ISSN 0928-0987
Abstract
To prepare the way for using the isotopically labelled SABRE hyperpolarised 4,6-d2-nicotinamide as an MRI agent in humans we have performed an in-vivo study to measure its pharmacokinetics in the plasma of healthy rats after intravenous and oral administration. Male Han Wistar rats were dosed with either 4,6-d2-nicotinamide or the corresponding control, non-labelled nicotinamide, and plasma samples were obtained at eight time points for up to 24 hours after administration. Pharmacokinetic parameters were determined from agent concentration-versus-time data for both 4,6-d2-nicotinamide and nicotinamide. 4,6-d2-nicotinamide proved to be well tolerated regardless of route of administration at the concentrations used (20, 80 and 120 mg/kg). Pharmacokinetic parameters were similar after oral and intravenous administration and similar to those obtained for nicotinamide. Analysis of nicotinamide plasma concentrations after dosing 4,6-d2-nicotinamide intravenously demonstrates a reversible exchange of endogenous nicotinamide by this labelled agent over the time-course of our assays. Supported by a large body of evidence for the safety of nicotinamide when dosed orally in humans, we conclude that 4,6-d2-nicotinamide can also be safely administered intravenously, which will provide significant benefit when using this agent for planned imaging studies in humans.
Metadata
Authors/Creators: |
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Copyright, Publisher and Additional Information: | Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved. | ||||||
Keywords: | SABRE, Hyperpolarisation, Deuteration, Pharmacokinetics, Nicotinamide, SABRE, Nicotinamide, Deuteration, Pharmacokinetics, Hyperpolarization | ||||||
Dates: |
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Institution: | The University of York | ||||||
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) | ||||||
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Depositing User: | Pure (York) | ||||||
Date Deposited: | 14 May 2019 09:30 | ||||||
Last Modified: | 06 Dec 2023 13:06 | ||||||
Published Version: | https://doi.org/10.1016/j.ejps.2019.05.004 | ||||||
Status: | Published | ||||||
Refereed: | Yes | ||||||
Identification Number: | https://doi.org/10.1016/j.ejps.2019.05.004 | ||||||
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