Pharmacokinetic Drug Interactions

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Abstract
MOST clinically observed drug interactions—both beneficial and adverse— are probably caused by additive, synergistic, or antagonistic effects of agents that act at the same site or on the same physiologic system. There has been more emphasis in the literature, however, on those interactions that occur when one drug affects the activity of another by altering its absorption, distribution, metabolism, or excretion (the so-called "pharmacokinetic,"1"ADME",2or "indirect"3interactions). These complex mechanisms have been extensively studied in laboratory animals, but less is known of their incidence or importance in man. The pharmacokinetic interactions of widely used drugs could be of major clinical importance. This review focuses on a commonly prescribed group, the sedative, hypnotic, and antianxiety agents. MECHANISMS OF INTERACTIONS Enhancement of Metabolism.— Most drugs and many naturally occurring compounds are metabolized into water-soluble derivatives before excretion, and this biotransformation is effected mainly by microsomal enzymes of the