In vitro metabolic stability of moisture-sensitive rabeprazole in human liver microsomes and its modulation by pharmaceutical excipients

Archives of Pharmacal Research
Shan RenBeom-Jin Lee

Abstract

A reliable method to assess in vitro metabolic stability of rabeprazole and its modulation by Generally Recognized As Safe (GRAS)-listed pharmaceutical excipients was established in human liver microsomes. The metabolic stability of rabeprazole decreased as a function of incubation time, resulting in the formation of thioether rabeprazole via nonenzymatic degradation and enzymatic metabolism. Buffer type was also a determining factor for the degree of both nonenzymatic degradation and enzymatic metabolism. The net extent of enzymatic drug metabolism, obtained by calculating the difference in drug degradation between a microsome-present reaction system and a microsome-free solution, was about 9.20 +/- 0.67% in phosphate buffer and 2.27 +/- 1.76% in Tris buffer, respectively. Rabeprazole exhibited first-order kinetics in microsome-free solution but showed non-linear kinetics in the microsome-present reaction system. The maximal velocity, Vmax, in phosphate buffer was 5.07 microg mL(-1) h(-1) and the Michaelis-Menten constant, Km, was 10.39 microg mL(-1) by computer-fitting to the classical Michaelis-Menten equation for pattern of time-dependent change in the substrate concentration. The intact drug and its thioether form were wel...Continue Reading

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Oct 12, 2007·International Journal of Pharmaceutics·Shan RenBeom-Jin Lee

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Citations

Aug 1, 2012·Nanomedicine : Nanotechnology, Biology, and Medicine·A Christy HunterS Moein Moghimi
Nov 4, 2008·International Journal of Pharmaceutics·Ae Ra KimBeom-Jin Lee
Mar 16, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Ranjeet Prasad DashNuggehally R Srinivas
Jul 14, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jie PuMingshe Zhu
Jun 20, 2019·Recent Patents on Nanotechnology·Dilpreet SinghNeena Bedi
Nov 7, 2020·International Journal of Molecular Sciences·Rahul PatelAmr ElShaer

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