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Pharmacokinetic and Metabolomic Studies with BIO 300, a Nanosuspension of Genistein, in a Nonhuman Primate Model

Genistein is a naturally occurring phytoestrogen isoflavone and is the active drug ingredient in BIO 300, a radiation countermeasure under advanced development for acute radiation syndrome (H-ARS) and for the delayed effects of acute radiation exposure (DEARE). Here we have assessed the pharmacokine...

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Autores principales: Cheema, Amrita K., Mehta, Khyati Y., Santiago, Paola T., Fatanmi, Oluseyi O., Kaytor, Michael D., Singh, Vijay K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429499/
https://www.ncbi.nlm.nih.gov/pubmed/30870965
http://dx.doi.org/10.3390/ijms20051231
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author Cheema, Amrita K.
Mehta, Khyati Y.
Santiago, Paola T.
Fatanmi, Oluseyi O.
Kaytor, Michael D.
Singh, Vijay K.
author_facet Cheema, Amrita K.
Mehta, Khyati Y.
Santiago, Paola T.
Fatanmi, Oluseyi O.
Kaytor, Michael D.
Singh, Vijay K.
author_sort Cheema, Amrita K.
collection PubMed
description Genistein is a naturally occurring phytoestrogen isoflavone and is the active drug ingredient in BIO 300, a radiation countermeasure under advanced development for acute radiation syndrome (H-ARS) and for the delayed effects of acute radiation exposure (DEARE). Here we have assessed the pharmacokinetics (PK) and safety of BIO 300 in the nonhuman primate (NHP). In addition, we analyzed serum samples from animals receiving a single dose of BIO 300 for global metabolomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS). We present a comparison of how either intramuscularly (im) or orally (po) administered BIO 300 changed the metabolomic profile. We observed transient alterations in phenylalanine, tyrosine, glycerophosphocholine, and glycerophosphoserine which reverted back to near-normal levels 7 days after drug administration. We found a significant overlap in the metabolite profile changes induced by each route of administration; with the po route showing fewer metabolic alterations. Taken together, our results suggest that the administration of BIO 300 results in metabolic shifts that could provide an overall advantage to combat radiation injury. This initial assessment also highlights the utility of metabolomics and lipidomics to determine the underlying physiological mechanisms involved in the radioprotective efficacy of BIO 300.
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spelling pubmed-64294992019-04-10 Pharmacokinetic and Metabolomic Studies with BIO 300, a Nanosuspension of Genistein, in a Nonhuman Primate Model Cheema, Amrita K. Mehta, Khyati Y. Santiago, Paola T. Fatanmi, Oluseyi O. Kaytor, Michael D. Singh, Vijay K. Int J Mol Sci Article Genistein is a naturally occurring phytoestrogen isoflavone and is the active drug ingredient in BIO 300, a radiation countermeasure under advanced development for acute radiation syndrome (H-ARS) and for the delayed effects of acute radiation exposure (DEARE). Here we have assessed the pharmacokinetics (PK) and safety of BIO 300 in the nonhuman primate (NHP). In addition, we analyzed serum samples from animals receiving a single dose of BIO 300 for global metabolomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS). We present a comparison of how either intramuscularly (im) or orally (po) administered BIO 300 changed the metabolomic profile. We observed transient alterations in phenylalanine, tyrosine, glycerophosphocholine, and glycerophosphoserine which reverted back to near-normal levels 7 days after drug administration. We found a significant overlap in the metabolite profile changes induced by each route of administration; with the po route showing fewer metabolic alterations. Taken together, our results suggest that the administration of BIO 300 results in metabolic shifts that could provide an overall advantage to combat radiation injury. This initial assessment also highlights the utility of metabolomics and lipidomics to determine the underlying physiological mechanisms involved in the radioprotective efficacy of BIO 300. MDPI 2019-03-12 /pmc/articles/PMC6429499/ /pubmed/30870965 http://dx.doi.org/10.3390/ijms20051231 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cheema, Amrita K.
Mehta, Khyati Y.
Santiago, Paola T.
Fatanmi, Oluseyi O.
Kaytor, Michael D.
Singh, Vijay K.
Pharmacokinetic and Metabolomic Studies with BIO 300, a Nanosuspension of Genistein, in a Nonhuman Primate Model
title Pharmacokinetic and Metabolomic Studies with BIO 300, a Nanosuspension of Genistein, in a Nonhuman Primate Model
title_full Pharmacokinetic and Metabolomic Studies with BIO 300, a Nanosuspension of Genistein, in a Nonhuman Primate Model
title_fullStr Pharmacokinetic and Metabolomic Studies with BIO 300, a Nanosuspension of Genistein, in a Nonhuman Primate Model
title_full_unstemmed Pharmacokinetic and Metabolomic Studies with BIO 300, a Nanosuspension of Genistein, in a Nonhuman Primate Model
title_short Pharmacokinetic and Metabolomic Studies with BIO 300, a Nanosuspension of Genistein, in a Nonhuman Primate Model
title_sort pharmacokinetic and metabolomic studies with bio 300, a nanosuspension of genistein, in a nonhuman primate model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429499/
https://www.ncbi.nlm.nih.gov/pubmed/30870965
http://dx.doi.org/10.3390/ijms20051231
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