Pharmacokinetics of the SABRE agent 4,6-d2-nicotinamide and also nicotinamide in rats following oral and intravenous administration
| العنوان: | Pharmacokinetics of the SABRE agent 4,6-d2-nicotinamide and also nicotinamide in rats following oral and intravenous administration |
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| المؤلفون: | Linnik, Inna V., Rayner, Peter J., Stow, Ruth A., Duckett, Simon B., Cheetham, Graham M.T. |
| المصدر: | European Journal of Pharmaceutical Sciences |
| بيانات النشر: | Elsevier Science B.V, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Niacinamide, LLOQ, Lower Limit of Quantification, Administration, Oral, Article, MRI, Magnetic Resonance Imaging, Tandem Mass Spectrometry, Deuteration, Animals, Pharmacokinetics, SABRE, Signal Amplification By Reversible Exchange, Infusions, Intravenous, Nicotinamide, Chromatography, High Pressure Liquid, SABRE, Dose-Response Relationship, Drug, NA, protio-nicotinamide, PO, per os (oral), d2-NA, 4,6-d2-nicotinamide, ULOQ, Upper Limit of Quantification, Deuterium, Rats, Hyperpolarization, Administration, Intravenous, IP, intraperitoneal, IV, intravenous |
| الوصف: | To prepare the way for using the isotopically labelled SABRE hyperpolarized 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 h 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. Graphical abstract Mean concentrations of (a) 4,6-d2-nicotinamide and (b) nicotinamide in the plasma of male rats following a single IV administration of 4,6-d2-nicotinamide at nominal dose levels of 20 mg/kg (Image 9), 60 mg/kg (Image 10) and 120 mg/kg (Image 11). Endogenous NA is released after intravenous administration of d2-NA.Unlabelled Image |
| اللغة: | English |
| تدمد: | 1879-0720 0928-0987 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid________::ee68f7c2b28c1c0f9184a32ba358fa63 http://europepmc.org/articles/PMC6556870 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.pmid..........ee68f7c2b28c1c0f9184a32ba358fa63 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18790720 09280987 |
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