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Pharmacogenetics in Immunosuppressive Therapy: The Best Thing Since TDM?

Pharmacogenomics refers to drug discovery based on knowledge of genes, whereas the term pharmacogenetics usually is applied for the (much older) field of how genetic differences influence the variability in patients’ responses to drugs. Although both terms are being used interchangeably, this paper has a strong focus on the latter discipline, and we limit ourselves to the use of pharmacogenetics. For reviews on the fundamentals of medical genetics and on the methods used in pharmacogenetics/-omics, and on discovery of new etiologic mechanisms, on drug target selection, or on highthroughput screening of chemical compounds, on proteomics or microarrays, we refer the reader to the literature. That for many drugs there is considerable interindividual variability in both pharmacokinetics and pharmacodynamics is a fact known for many years. In fact, the entire discipline of therapeutic drug monitoring (TDM) is largely based on the difficulty of predicting drug concentrations in whole blood or plasma with standard dose or body weight-adjusted dose drug treatment. By monitoring drug concentrations and adjusting drug dosages to reach predefined target levels, toxic or ineffective concentrations can be avoided.