The chemical properties of alicyclic heterocycles are similar to those of the corresponding chain compounds. Compound: (S)-3-((S)-2-(((S)-1-Ethoxy-1-oxo-4-phenylbutan-2-yl)amino)propanoyl)-1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride, is researched, Molecular C20H28ClN3O6, CAS is 89396-94-1, about Analysis of Intra- and Intersubject Variability in Oral Drug Absorption in Human Bioequivalence Studies of 131 Generic Products, the main research direction is oral drug absorption variability human bioequivalence; BCS; CYP3A4; bioequivalence; intrasubject variability; solubility-limited absorption.Name: (S)-3-((S)-2-(((S)-1-Ethoxy-1-oxo-4-phenylbutan-2-yl)amino)propanoyl)-1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride.
In this study, the data of 113 human bioequivalence (BE) studies of immediate release (IR) formulations of 74 active pharmaceutical ingredients (APIs) conducted at Sawai Pharmaceutical Co., Ltd., was analyzed to understand the factors affecting intra- and intersubject variabilities in oral drug absorption. The ANOVA CV (%) calculated from area under the time-concentration curve (AUC) in each BE study was used as an index of intrasubject variability (Vintra), and the relative standard deviation (%) in AUC was used as that of intersubject variability (Vinter). Although no significant correlation was observed between Vintra and Vinter of all drugs, Vintra of class 3 drugs was found to increase in association with a decrease in drug permeability (Peff). Since the absorption of class 3 drugs was rate-limited by the permeability, it was suggested that, for such drugs, the low Peff might be a risk factor to cause a large intrasubject variability. To consider the impact of poor water solubility on the variability in BE study, a parameter of Peff/Do (Do; dose number) was defined to discriminate the solubility-limited and dissolution-rate-limited absorption of class 2 drugs. It was found that the class 2 drugs with a solubility-limited absorption (Peff/Do < 0.149×10-4 cm/s) showed high intrasubject variability. Furthermore, as a reason for high intra- or intersubject variability in AUC for class 1 drugs, effects of drug metabolizing enzymes were investigated. It was demonstrated that intrasubject variability was high for drugs metabolized by CYP3A4 while intersubject variability was high for drugs metabolized by CYP2D6. For CYP3A4 substrate drugs, the Km value showed the significant relation with Vintra, indicating that the affinity to the enzyme can be a parameter to predict the risk of high intrasubject variability. In conclusion, by analyzing the in house data of human BE study, low permeability, solubility-limited absorption, and high affinity to CYP3A4 are identified as risk factors for high intrasubject variability in oral drug absorption. This information is of importance to design the human BE study for oral drug products containing APIs with a risk of large intrasubject variability in oral absorption. Compound(89396-94-1)Name: (S)-3-((S)-2-(((S)-1-Ethoxy-1-oxo-4-phenylbutan-2-yl)amino)propanoyl)-1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride received a lot of attention, and I have introduced some compounds in other articles, similar to this compound((S)-3-((S)-2-(((S)-1-Ethoxy-1-oxo-4-phenylbutan-2-yl)amino)propanoyl)-1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride), if you are interested, you can check out my other related articles.
Reference:
Copper catalysis in organic synthesis – NCBI,
Special Issue “Fundamentals and Applications of Copper-Based Catalysts”