In drug metabolism

A slightly different use of accurate mass measurement in drug metabolism studies has been reported [31]. In this investigation, the accurate masses of the ions derived from Glyburide (Figure 5.48) and some of its metabolites were used to calculate the difference in mass, and thus the elemental composition, between certain of the ions observed in the spectra of the various compounds. 

Walker, C.H. (1980). Species variations in some hepatic microsomal enzymes that metabolise xenobiotics. Progress in Drug Metabolism 5, 118-164. 

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

Lewis DFV. Structural characteristics of human P450s involved in drug metabolism QSARs and lipophilicity profiles. Toxicology 2000 144 197-203. 

Lewis DF, Jacobs MN, Dickins M. Compound lipophilicity for substrate binding to human P450s in drug metabolism. Drug Discov Today 2004 9 530-7. 

White JF, Carlson GP. 1979. Influence of alterations in drug metabolism on spontaneous and epinephrine-induced cardiac arrhythmias in animals exposed to trichloroethylene. Toxicol Appl Pharmacol 47 515-527. 

Van de Waterbeemd, H. High-throughput and in silico techniques in drug metabolism and pharmacokinetics. Curr. Opin. Drug Dis. Dev. 2002, 5, 33-43. 

J. M. Hutzler, T. S. Tracy 2002, (Atypical kinetic profiles in drug metabolism reactions), Drug Metab. Dispos. 30(4), 355. 

CYP2C19 is another example of the existence of both cross-ethnic and inter-individual variations in drug metabolism. This enzyme is involved in the metabolism of many psychotropics such as diazepam and tertiary tricyclic antidepressants, as well as one of the selective serotonin re-uptake inhibitors (SSRIs), citalopram. Using S-mephenytoin as the probe, previous studies showed that up to 20% of East Asians (Chinese, Japanese, and Koreans) are PMs, when only 3-5%... 

Branch, R. A., Salih, S. Y. el al. (1978). Racial differences in drug metabolizing ability a study with antipyrine in the Sudan. Clin. Pharmacol. Ther., 24(3), 283-6. 

Guengerich, F. P. (1999). Cytochrome P-450 3A4 regulation and role in drug metabolism. Annu. Rev. Pharmacol. Toxicol, 39, 1-17. 

Lou, Y.C. (1990). Differences in drug metabolism polymorphism between Orientals and Caucasians. DrugMetab. Rev., 22, 451-75. 

Concepts in Drug Metabolism (in two parts), edited by Peter Jenner and Bernard Testa... 

Solute uptake can also be evaluated in isolated cell suspensions, cell mono-layers, and enterocyte membrane vesicles. In these preparations, uptake is normalized by enzyme activity and/or protein concentration. While the isolation of cells in suspension preparations is an experimentally easy procedure, disruption of cell monolayers causes dedifferentiation and mucosal-to-serosal polarity is lost. While cell monolayers from culture have become a popular drug absorption screening tool, differences in drug metabolism and carrier-mediated absorption [70], export, and paracellular transport may be cell-type- and condition-depen-dent. 

Although there are many enzymes involved in drug metabolism, the in vitro systems containing CYPs and UGTs are often used for metabolite synthesis due to the reasons discussed before. 

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... 

Rushmore, T.H., Reider, P.J., Slaughter, D. et al. (2000) Bioreactor systems in drug metabolism synthesis of cytochrome P450-generated metabolites. Metabolic Engineering, 2, 115-125. 

An important part of the optimization process of potential leads to candidates suitable for clinical trials is the detailed study of the absorption, distribution, metabolism and excretion (ADME) characteristics of the most promising compounds. Experience has learned that physico-chemical properties play a key role in drug metabolism and pharmacokinetics (DMPK) [1-3]. As an example, physicochemical properties relevant to oral absorption are described in Fig. 1.1. It is important to note that these properties are not independent, but closely related to each other. 

Eichelbaum, M., Burk, O., CYP3A genetics in drug metabolism, Nature Med. 2001, 7, 285-287. 

Nebert DW. Polymorphisms in drug-metabolizing enzymes what is their clinical relevance and why do they exist Am J Hum Genet 1997 60 265-271. 

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