By A. David Rodrigues
ISBN-10: 0585407061
ISBN-13: 9780585407067
ISBN-10: 0824702832
ISBN-13: 9780824702830
This reference offers entire assurance of the preclinical, medical, toxicological, regulatory, and advertising and marketing views of metabolism-based drug-drug interactions-relating pharmacokinetic suggestions to Michaelis-Menten kinetics. The booklet presents worthwhile examples, consultant enzyme structures, and computer-aided modeling to elucidate key recommendations. It deals approximately 2 hundred precious tables, equations, drawings, and pictures, and contributions via world-renowned specialists within the box. They talk about kinetics-based in vitro-in vivo correlations, tools for the advance of a metabolic drug interplay (MDI) database, and extra.
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Additional resources for Drug - Drug Interactions (Drugs and the Pharmaceutical Sciences)
Sample text
C. Reaction Conditions In addition to the preceding complexities, the P450 enzymes have some unique characteristics that complicate the design of experimental protocols. Due to the broad substrate selectivities for these enzymes, the enzymes are not optimized for the metabolism of a particular substrate. ) that result in optimum velocities for a given reaction are dependent on both the enzyme and the substrate. To further complicate matters, the velocities for these enzymes tend to vary greatly with changes in these reaction conditions.
The expected effect of a combination of agents. J. Theor. Biol. 114:413–431, 1985. 2 In Vitro Enzyme Kinetics Applied to Drug-Metabolizing Enzymes Kenneth R. Korzekwa Camitro Corporation, Menlo Park, California I. INTRODUCTION Most new drugs enter clinical trials with varying amounts of information on the human enzymes that may be involved in their metabolism. Most of this information is obtained from (1) animal studies, (2) human tissue preparations in conjunction with chemical inhibitors or antibodies, and (3) expressed enzymes.
Clearly, events at steady state depend only on clearance, while the time course on approach to the plateau is governed only by k, and hence half-life, information known from a single-dose study. 3 half-lives. Accordingly, drugs with short half-lives will reach steady state quickly, and those with half-lives in the order of days will take over a week. Hence, knowing the t 1/2 of a drug is important when planning the duration of a study and the frequency of sampling of blood to characterize kinetic events.