Drug metabolism intestinal

To correctly predict overall oral absorption, drug metabolism in intestinal epithelial cells by cytochrome P450 enzymes should also be considered. The prediction of drug metabolism has already been covered in detail in Chapter 18. 

The gastrointestinal microflora provide another potential site for drug metabolism within the GIT, and it has received some attention. In normal subjects the stomach and proximal small intestine contain small numbers of microorganisms. Concentrations of these organisms increase toward the distal end of the intestine. A wide variety of aerobic and anaerobic organisms are present in the gut. The microflora, derived primarily... 

LZ Benet, CY Wu, MF Hebert, VJ Wacher. Intestinal drug metabolism and antitransport processes A potential paradigm shift in oral drug delivery. J Controlled Release 39 139-143, 1996. 

The pharmacokinetics of rifaximin after oral administration has been studied in healthy volunteers and patients with intestinal infections or IBD. The aim of these studies was to confirm the low, if any, systemic absorption of the drug metabolism and excretion data are scant. In all these investigations a sensitive high-pressure liquid chromatographic (HPLC) method was used to measure rifaximin in body fluids. 

The original humanized mice bear the expression hPXR exclusively in the liver [10]. As both drug-metabolizing enzymes and xenobiotic receptors are also highly expressed in the intestinal tracts, it is conceivable that mouse models with the humanized receptors expressed in both the liver and the intestine would represent a... 

Benet LZ, Wu CY, Hebert MF and Wacher VJ (1996) Intestinal Drug Metabolism and Anti-Transport Processes A Potential Paradigm Shift in Oral Drug Delivery. 

Keywords Intestinal drug absorption Intestinal metabolism Cell culture-based models Membrane-based models Ex vivo models... 

Intestinal Metabolism Intestinal drug metabolism can occur by microflora present in the gut lumen, as well as by enzymes present in luminal fluids and in the intestinal mucosa [166], Metabolism of xenobiotics by gut microflora is low in comparison to metabolism by the gut mucosa and liver [62], However, the intestinal microflora (e.g., Bacteroides and Bifidobacteria) may play an important role in the first-pass metabolism of compounds that are poorly or incompletely absorbed by the gut mucosa, especially in the lower parts of the intestine. This bacterial metabolism is largely degradative,... 

Drugs can be metabolized either in the intestinal lumen or in the intestinal wall. The most common approach to determine drug metabolism in the intestinal lumen is by direct incubation with bacterial preparations, which can be gut content or pure culture of organisms of the GI tract of various mammalian species [62],... 

K. Hosoya, M. Tomi, M. Takayama, Y. Komokata, D. Nakai, T. Tokui, K. Nishimura, M. Ueda, M. Obinata, S. Hori, S. Ohtsuki, G. L. Amidon, and T. Terasaki. Transporter mRNA expression in a conditionally immortalized rat small intestine epithelial cell line (TR-SIE). Drug Metabol. Pharmacokinet. 19 264-269 (2004). 

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