Variability In Drug Handling And Adverse Drug Reactions

ADRs can occur as a result of variability in either the pharmacokinetic and/or pharmacodynamic properties of drugs (Fig. 1). Some examples of how genetically determined variation in pharmacokinetics (absorption, distribution, metabolism, and excretion) can lead to ADRs are shown in Table 1. Genetically determined variation in pharmacodynamic properties of drugs leading to ADRs has been less well studied than pharmacokinetic variation and may in many cases represent a predominant risk factor (Table 2). With the completion of the human genome project and the identification of genetic variability in drug targets, this represents a fruitful area of research. Genetic factors leading to ADRs have been the subject of many reviews (7,23-32) to which the readers should refer and are also mentioned in other chapters in this book. In this chapter, we have concentrated on recent advances, pointing out where possible the strengths and weaknesses. We also cover the difficult area of what steps will be required before pharmacogenetics can be incorporated into clinical practice in order to reduce the burden of ADRs.

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