Enzymes are biological catalysts that produce large increases in reaction rates and tend to be specific for certain reactants and products. 16251-45-9, Name is (4S,5R)-4-Methyl-5-phenyloxazolidin-2-one, molecular formula is C10H11NO2, belongs to oxazolidines compound. In a document, author is Obach, R. Scott, introduce the new discover, Recommanded Product: (4S,5R)-4-Methyl-5-phenyloxazolidin-2-one.
Estimation of Circulating Drug Metabolite Exposure in Human Using In Vitro Data and Physiologically Based Pharmacokinetic Modeling: Example of a High Metabolite/Parent Drug Ratio
(R)-4-((4-(((4-((tetrahydrofuran-3-yl)-oxy) benzo[d] isoxazol-3-yl) oxy)methyl) piperidin-1-yl) methyl) tetrahydro-2H-pyran-4-ol (TBPT), a serotonin-4 receptor partial agonist, is metabolized to two metabolites: an N-dealkylation product [(R)-3-(piperidin-4-ylmethoxy)-4(( tetrahydrofuran-3-yl) oxy) benzo[d] isoxazole (M1)] and a cyclized oxazolidine structure [7-(((4-(((R)-tetrahydrofuran-3-yl) oxy) benzo [d] isoxazol-3-yl) oxy) methyl) octahydro-3H (M2)]. After administration of TBPT to humans the exposure to M1 was low and the exposure to M2 was high, relative to the parent drug, despite this being the opposite in vitro. In this study, projection of the plasma metabolite/parent (M/P) ratios for M1 andM2 was attempted using in vitro metabolism, binding, and permeability data in static and dynamic physiologically based pharmacokinetic (PBPK) models. In the static model, the fraction of parent clearance yielding the metabolite (which also required taking into account secondary metabolites of M1 and M2), the clearance of the metabolites and parent, and an estimate of the availability of the metabolites from the liver were combined to yield estimated parent/metabolite ratios of 0.32 and 23 for M1 and M2, respectively. PBPK modeling that used in vitro and physicochemical data input yielded estimates of 0.26 and 20, respectively. The actual values were 0.12 for M1/TBPT and 58 for M2/TBPT. Thus, the ratio for M1 was overpredicted, albeit at values less than unity. The ratio for M2/TBPT was underpredicted, and the high ratio of 58 may exceed a limiting ceiling of the approach. Nevertheless, when considered in the context of determining whether a potential circulating metabolite may be quantitatively important prior to administration of a drug for the first time to humans, the approaches succeeded in highlighting the importance of M2 (M/P ratio >> 1) relative to M1, despite M1 being much greater than M2 in vitro.
Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law. In my other articles, you can also check out more blogs about 16251-45-9. Recommanded Product: (4S,5R)-4-Methyl-5-phenyloxazolidin-2-one.
Reference:
Oxazolidine – Wikipedia,
,Oxazolidine | C3H7NO – PubChem