Susceptibility of the H2-receptor antagonists cimetidine, famotidine and nizatidine, to metabolism by the gastrointestinal microflora

How to Determine the Role of the Microbiome in Drug Disposition

“…This method has the advantage of capturing a greater diversity of organisms and has been successfully applied to identify numerous drugs that are susceptible to microbial metabolism (Valerino et al, 1972;Caldwell and Hawksworth, 1973;Smith and Griffiths, 1974;Powis et al, 1979;Koch and Goldman, 1979;Koch et al, 1980;Lindenbaum et al, 1981;Elmer and Remmel, 1984;Harris et al, 1986;Strong et al, 1987;Shu et al, 1991;DH Kim et al, 1992;Lavrijsen et al, 1995;Watanabe et al, 1995;Kitamura et al, 1997;Sasaki et al, 1997;Basit and Lacey, 2001;Basit et al, 2002;Deng et al, 2011;Li et al, 2012;McCabe et al, 2015). However, when testing a community of microorganisms collectively, inter-strain antagonism may mask This article has not been copyedited and formatted.…”

Biotransformation studies of prednisone using human intestinal bacteria Part II: Anaerobic incubation and docking studies

“…The result of prediction is presented as a list of activities with appropriate Pa (probability as active) and Pi (probability as inactive), sorted in descending order. (3)(4)(5)(6)(7)(8)(9) were constructed using the builder interface of the MOE program and subjected to energy minimization using the included MOPAC 7.0 tool. The model produced was then subjected to systematic conformational search, where all items were set as default with a root mean square (RMS) gradient of 0.01 kcal/mol and RMS distance (RMSD) of 0.1 Å.…”

“…The isolated steroidal metabolites (3)(4)(5)(6)(7)(8)(9) were screened for prediction of the possible biological activities at levels of more than 75% probability. The results afforded a valuable guide for further study of the undesirable side effects and/or favorable activities of the metabolites.…”

“…A detailed description of the microbial transformation of steroids has been reviewed by Lizuka and Natio 5 . In many studies, feces have served as a sample of the gastrointestinal flora [6][7][8] . The vast majority (99.9%) of the estimated 400 different bacterial species in the human colon are strict anaerobes.…”

“…In the present article, we report the isolation and structural determination of nine metabolites obtained after anaerobic incubation of 1 with a fecal bacterial mixture from a human subject. Furthermore, the potential inhibitory activity of the isolated metabolites (3)(4)(5)(6)(7)(8)(9) as substrates for prostaglandin E2 9-ketoreductase (PGE2 9-KR) has been studied using the computerized system PASS (Prediction of Activity Spectra for Substance). The docking of prednisone 1 and its respective metabolites (3)(4)(5)(6)(7)(8)(9) has also been investigated since these structures are of most relevance for PGE2 9-KR enzyme inhibition.…”