Mammalian drug metabolism model

O. Corcoran, J.C. Lindon, R. Hall, I.M. Ismail, J.K. Nicholson, The potential of F-19 NMR spectroscopy for rapid screening of cell cultures for models of mammalian drug metabolism. Analyst 126 (2001) 2103-2106. 

Metabolism studies are essential for approval of any clinically useful drug. Microorganisms have been successfully used as in vitro models for prediction of mammalian drug metabolism due to the significant similarity of certain microbial enzyme systems, specifically fungi, with mammalian liver enzyme systems.66 The following metabolism study represents the first for a cembranoid diterpene and may aid future development of other cembranoids as clinically useful drugs. 

Griffiths, D.A., Best, D.J., Jezequel, S.G. The screening of selected microorganisms for use as models of mammalian drug metabolism. Appl. Microbiol. Biotechnol. 1991, 35 373-381. 

Talafous J, Sayre LM, Mieyal JJ, Klopman G. META. 2. A dictionary model of mammalian xenobiotic metabolism. J Chem Inf Comput Sci 1994 34 1326-33. Klopman G, Tu M, Talafous J. META. 3. A genetic algorithm for metabolic transform priorities optimization. J Chem Inf Comput Sci 1997 37 329-34. Langowski J, Long A. Computer systems for the prediction of xenobiotic metabolism. Adv Drug Del Rev 2002 54 407-15. 

In the 1970s, Smith and Rosazza introduced the concept of microbial models of mammalian metabolism [38,39]. Two reviews in this area were published in 1999 [40,41]. Since these, there have been numerous reports describing the use of microbial biotransformation in drug metabolism studies [42-54]. These reports demonstrated that microbial enzymes were able to... 

Rao, G.P. and Davis, P.J. (1997) Microbial models of mammalian metabolism biotransformation of HP 749 (besipirdine) using Cunninghamella elegans. Drug Metabolism and Disposition The Biological Fate of Chemicals, 25, 709-715. 

Teissier E, Fennrich S, Strazielle N, Daval JL, Ray D, et al. 1998. Drug metabolism in in vitro organotypic and cellular models of mammalian central nervous system activities of membrane-bound epoxide hydrolase and NADPH-cytochrome P-450 (c) reductase. Neurotoxicology 19 347-355. 

The use of microbial systems as in vitro models for drug metabolism in humans has been proposed, as there are many similarities between certain microbial enzyme systems and mammalian liver enzyme systems. The major advantages of using microorganisms are their ability to produce significant quantities of metabolites that would otherwise be difficult to obtain from animal systems or by chemical synthesis, and the considerable reduction in operating costs compared with animal studies. 

Moussa C et al. (1997) Microbial models of mammalian metabolism. Fungal metabolism of phenolic and nonphenolic p-cymene-related drugs and prodrugs. 11. Metabolites of nonphenolic derivatives. Drug Metab Dispos 25(3) 311-316... 

The degree of exposure of the fetus to a particular substance can be best assessed in human subjects, but concerns of fetal safety have restricted the use of this approach. Moreover, clinical studies cannot elucidate the various mechanisms that contribute to transplacental transport of a particular compound. There are many structural differences between the human placenta and the placenta of other mammalian species, which complicates extrapolation of data obtained from in vivo animal models to humans [7], Thus, several ex vivo and in vitro techniques have been developed to study the placental role in drug transfer and metabolism during pregnancy and there are some excellent articles that discuss these systems in detail [7], Both isolated tissues and various cell culture techniques are currently in use and these have been summarized below. 

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