Model drug metabolism

Zurek J, Harvey JN, Mulholland AJ. Modelling drug metabolism in cytochrome P450 enzymes. 2006 ISQBP President s Meeting, Strasbourg. 2006. 

An entirely different type of software advance is in the area of modeling drug metabolizing enzymes to predict whether a discovery compound will be a substrate for a particular enzyme for example, the polymorphic enzyme CYP2D6 [123,124]. In addition, software companies, such as Camitro Corp (see Chap 1), are developing software to predict the site(s) and rates of oxidative metabolism by modeling the major cytochrome P450 enzymes. Both of these innovative approaches allow thousands of compounds to be screened in a virtual environment with minimal use of laboratory experiments to make decisions. 

Doran, A., Obach, R.S., Smith, B.J., Hosea, N.A., Becker, S., Callegari, E., Chen, C., Chen, X. et al. (2005) The impact of P-glycoprotein on the disposition of drugs targeted for indications of the central nervous system evaluation using mdrla/lb knockout mouse model. Drug Metabolism and Disposition, 33, 165-174. 

Lindstrom, F.T. and Birkes, D.S. Estimation of population pharmacokinetic parameters using destructively obtained experimental data A simulation study of the 1-compartment open model. Drug Metabolism Reviews 1984 15 195-264. 

Mager, D.E., Wyska, E., and Jusko, W.J. Diversity of mechanism-based pharmacodynamic models. Drug Metabolism and Disposition 2003 31 510-519. 

Steimer, J.-L., Mallet, A., Golmard, J.-L., and Boisvieux, J.-F. Alternative approachs to estimation of population pharmacokinetic parameters Comparison with the nonlinear mixed-effect model. Drug Metabolism Reviews 1984 15 265-302. 

Korolev D, Balakin KV, Nikolsky Y, Kirillov E, Ivanenkov YA, Savchuk NP, Ivashchenko A A, Nikolskaya T. Modeling of human cytochrome p450-mediated drug metabolism using unsupervised machine learning approach. J Med Chem 2003 46 3631-43. 

Shen M, Xiao Y, Golbraikh A, Gombar VK, Tropsha A. Development and validation of k-nearest-neighbor QSPR models of metabolic stability of drug candidates. J Med Chem 2003 46 3013-20. 

Statistical, Pharmacophore, and Homology Models and Crystal Structures of Drug-Metabolizing Enzymes... 

STATISTICAL, PHARMACOPHORE, AND HOMOLOGY MODELS AND CRYSTAL STRUCTURES OF DRUG-METABOLIZING ENZYMES... 

TABLE 18.1 Human Enzymes Involved in Drug Metabolism That Have Been Computationally Modeled to Date... 

Bugrim A, Nikolskaya T, Nikolsky Y. Early prediction of drug metabolism and toxicity systems biology approach and modeling. Drug Discov Today 2004 9 127-35. 

Berellini G, Cruciani G, Mannhold R. Pharmacophore, drug metabolism, and pharmacokinetics models on non-peptide ATi, AT2, and AT1/AT2 angiotensin II receptor antagonists. J Med Chem 2005 48 4389-99. 

LIU Y and HU m (2002) Absorption and metabolism of flavonoids in the caco-2 cell culture model and a perfused rat intestinal model. Drug Metab Dispos. 30 (4) 370-77. 

Azerad R (1999) Microbial models for drug metabolism. Adv Biochem Eng Biotechnol 63 169-218... 

Lacroix 1, Biton J, Azerad R (1999) Microbial models of drug metabolism microbial transformations of trimegestone (RU 27987), a 3-keto-delta(4,9(10))-19-norsteroid drug. Bioorg Med Chem 7(11) 2329-2341... 

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... 

Azerd, R. (1999) Microbial models for the drug metabolism. Advances in Biochemical Engineering/Biotech-nology, 63, 169-218. 

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. 

Lacroix, I., Biton, J. and Azerad, R. (1999) Microbial Models of drug metabolism microbial transformations of Trimegestone (RU27987), a 3-keto-A4 9 101-19-norstcroid drug. Bioorganic and Medicinal Chemistry, 7, 2329-2341. 

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