Kinetics of Drug-Drug Interactions

  • Malcolm Rowland


Open any current medical journal and one is reminded that the coadministration of two or more drugs can either cause deleterious effects or lead to ineffective therapy. Those concerned with drug therapy are increasingly aware of this phenomenon but are confronted with the problem that a patient may be taking three, four, and, on occasion, even more drugs simultaneously. The computer will aid in the storage and retrieval of such information and act as a useful early warning signal, but prudent multiple drug therapy, if deemed necessary, can only be achieved with a better understanding of the nature and quantitative aspects of drug interactions. A drug interaction might broadly be defined as any reaction between one drug and another substance within or out of the body. In this review, the definition is restricted to events occurring within living systems with major emphasis on the alteration by one drug on the rate and extent of absorption, distribution, metabolism, and excretion of another. Prescott (1969) has called these “pharmacokinetic interactions” to distinguish them from the numerous interactions between drugs at their sites of action (Morrelli, 1970). This distinction is somewhat arbitrary as any or all possibilities can occur in vivo. The interaction may be direct, such as the competitive inhibition of drug metabolism and the displacement of a drug from binding sites, or it may be indirect. One example of the latter is the decreased renal clearance of acids, whose renal clearance is sensitive to urinary pH, produced when the urine is rendered alkaline using either the carbonic anhydrase inhibitor, acetazolamide, or sodium bicarbonate.


Drug Interaction Carbonic Anhydrase Inhibitor Plateau Level Unbind Concentration Warfarin Concentration 
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Copyright information

© Springer Science+Business Media New York 1972

Authors and Affiliations

  • Malcolm Rowland
    • 1
  1. 1.School of PharmacyUniversity of CaliforniaSan FranciscoUSA

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