Genistein is a naturally occurring phytoestrogen isoflavone and is the active drug ingredient\nin BIO 300, a radiation countermeasure under advanced development for acute radiation syndrome\n(H-ARS) and for the delayed effects of acute radiation exposure (DEARE). Here we have assessed\nthe pharmacokinetics (PK) and safety of BIO 300 in the nonhuman primate (NHP). In addition, we\nanalyzed serum samples from animals receiving a single dose of BIO 300 for global metabolomic\nchanges using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass\nspectrometry (QTOF-MS). We present a comparison of how either intramuscularly (im) or orally\n(po) administered BIO 300 changed the metabolomic profile. We observed transient alterations in\nphenylalanine, tyrosine, glycerophosphocholine, and glycerophosphoserine which reverted back to\nnear-normal levels 7 days after drug administration. We found a significant overlap in the metabolite\nprofile changes induced by each route of administration; with the po route showing fewer metabolic\nalterations. Taken together, our results suggest that the administration of BIO 300 results in metabolic\nshifts that could provide an overall advantage to combat radiation injury. This initial assessment\nalso highlights the utility of metabolomics and lipidomics to determine the underlying physiological\nmechanisms involved in the radioprotective efficacy of BIO 300.
Loading....