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By A. David Rodrigues
Authored by way of popular leaders within the box, this entire quantity covers all elements of drug-drug interactions, together with preclinical, medical, toxicological, and regulatory views. completely up-to-date, this moment version displays the numerous advances and contains wide new fabric on: key interaction among transporters and enzymes in drug metabolism and drug interactions the imperative function of pharmacogenetics in metabolism-based drug-drug interactions in vivo – in vitro correlations (reversible, mechanism-based inhibition, induction) in silico ways allowing structure-activity and structure-function reviews high-throughput screening and GLP equipment for comparing drug interactions in vitro using transgenic animal types to guage drug interactions supplying beneficial case examples and computer-aided modeling, Drug-Drug Interactions is stuffed with over 2 hundred valuable tables, equations, and figures to explain key options, and comprises serious new up-to-date info.
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Additional info for Drug-Drug Interactions, Second Edition (Drugs and the Pharmaceutical Sciences)
Sample text
Only when the concentration of one of the drugs approaches the molar concentration of the binding sites will substantial displacement occur. In practice, because most drugs are relatively potent, this displacement does not occur as often as one might have supposed, given so relatively few specific binding sites on plasma proteins. Even when substantial displacement does occur, it often is of little to no therapeutic importance. As seen from Eq. (13) (and Fig. 7) and emphasized in Eq. (16), an increase in fu will only increase CL of drugs with a low extraction ratio, such as warfarin.
This constraint ensures that accurate substrate concentration data are available for the kinetic analyses and minimizes the probability that product inhibition of the reaction will occur. This constraint can be problematic when the Km of the reaction is low, since the amount of product (10% of a low substrate concentration) may be below that needed for accurate product quantitation. One method to increase the substrate amount available is to use larger incubation volumes. For example, a 10-mL incubation has 10 times more substrate available than a 1-mL incubation.
Now, recognizing that Vm is directly proportional to the total amount of the respective enzyme and that induction involves an increase in its synthesis that increases the amount of the enzyme, it follows that the intrinsic clearance of the affected enzyme, and hence total CLint, also increases during induction. Examination of Eqs. 3d] [17/12/07/12:9:37] [1–30] Introducing Pharmacokinetic and Pharmacodynamic Concepts 11 influence of induction itself. These relationships between CL, E, Q, fu, and CLint are displayed graphically in Figure 7.