Drug Metabolism in Drug Design and Development Basic Concepts and Practice
versus fraction metabolized in relation to the ratio of [I]/Ki. The lines labeled 1, 2, and 3 represent increasing ratios (i.e., ...
(e.g., Phase II or renal excretion), then, the likelihood of a drug interaction is reduced and even large [I]/Kiratios become ir ...
effects for a drug with a narrow therapeutic window. With the expectation to harmonize and/or standardize clinical DDI studies, ...
St. John’s wort is a common herbal remedy for the treatment of depression and contains a complex mixture of components that can ...
state plasma concentrations of CBZ decline over this period, reaching a lower plateau after several weeks (Bertilsson et al., 19 ...
the cytosol and nucleus, is activated once a ligand binds, then corepressors (R) are removed and coactivators (A) recruited. At ...
cytoplasm by chaperone proteins, such as HSP90, in order to keep its transcriptional activity at constitutive levels. Translocat ...
5.3.3 Induction Models The number of models to evaluate induction of drug-metabolizing enzymes has increased tremendously over t ...
5.4 Reaction Phenotyping For any established drug or a NCE, it is important to understand the routes of elimination, the contrib ...
pathways (such as CYP3A4 by ketoconazole) would render this subpopulation at a much greater risk for adverse events when a drug ...
and/or immunoquantitated levels of individual CYP forms. More integrated systems, such as primary hepatocytes or precision-cut l ...
5.4.3 Clinical Evaluation The cost of clinical investigations, safety and regulatory concerns would likely prohibit the developm ...
mechanism-based inactivator of CYP2C8 (Ogilvie et al., 2006; Shitara et al., 2004). Therefore, the impact of gemfibrozil on ceri ...
Chien JY, Thummel KE, Slattery JT. Pharmacokinetic consequences of induction of CYP2E1 by ligand stabilization. Drug Metab Dispo ...
Handschin C, Meyer UA. Induction of drug metabolism: the role of nuclear receptors. Pharmacol Rev 2003;55:649–673. Hebert MF, Ro ...
LeCluyse EL. Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. Eur J Ph ...
Niemi M, Backman JT, Juntti-Patinen L, Neuvonen M, Neuvonen PJ. Coadministration of gemfibrozil and itraconazole has only a mino ...
Segel I. Enzyme Kinetics: Behaviour and Analysis of Rapid Equilibrium and Steady State Enzyme Systems. New York: Wiley Interscie ...
Xie W, Barwick JL, Downes M, Blumberg B, Simon CM, Nelson MC, Neuschwander- Tetri BA, Brunt EM, Guzelian PS, Evans RM. Humanized ...
6 DRUG TRANSPORTERS IN DRUG DISPOSITION, DRUG INTERACTIONS, AND DRUG RESISTANCE CINDYQ. XIA,JOHNNYJ. YANG,ANDSURESHK. BALANI 6.1 ...
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