Pharmacokinetics of the SABRE agent 4,6-d2-Nicotinamide and also Nicotinamide in rats following oral and intravenous administration

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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.
Original languageEnglish
Article numberEJPS-D-19-00374R1
Pages (from-to)32-37
Number of pages6
JournalEuropean journal of pharmaceutical sciences
Early online date9 May 2019
Publication statusPublished - 1 Jul 2019

Bibliographical note

Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.


  • SABRE, Hyperpolarisation, Deuteration, Pharmacokinetics, Nicotinamide
  • Nicotinamide
  • Deuteration
  • Pharmacokinetics
  • Hyperpolarization

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