Current Drug Metabolism

Michael Sinz
Bristol Myers Squibb
Wallingford, CT


Pharmacokinetic and Pharmacodynamic Variability: A Daunting Challenge in Drug Therapy

Author(s): Jiunn H. Lin

Affiliation: Department of Preclinical Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania USA.


Patients vary considerably in their response to drug therapy. A drug that proves to be pharmacologically effective in some patients at a given dose may be ineffective or even toxic in others. The interindividual variability in drug response represents a major challenge in drug therapy, particularly for drugs with narrow therapeutic index. The intensity and duration of a drug action are determined not only by pharmacokinetic processes, but also by pharmacodynamic processes. Therefore, the variability in drug response is a result of the variability in either pharmacokinetic or pharmacodynamic processes, or a combination of both. The purpose of this paper is to review the sources that contribute to pharmacokinetic and pharmacodynamic variability. Although the main focus will be on the genetic variability, the impact of environmental factors on drug response will also be discussed. Finally, the application and limitation of the concept of personalized medicine will be briefly discussed.

Keywords: Butyrylcholinesterase, N-Acetyltransferase polymorphism, CYP 2D6, UDP-Glucuronosyltransferases, Drug Transporters

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Article Details

Page: [109 - 136]
Pages: 28
DOI: 10.2174/138920007779816002
Price: $58