Foreword

Pharmacogenetics seeks to determine how a person's genetic makeup affects their response to medicines. Rapid advances in genetic technologies have opened up the possibility of genetic testing on a large scale at an affordable cost, thus facilitating the exploitation of pharmacogenetics not only in assessing risks, benefits, and indications of medicines, but also as a valuable tool in drug discovery.

Since the beginning of modern drug therapy, it has been realized that dose is a poor predictor of therapeutic response and that there is substantial variability in both therapeutic efficacy and the occurrence of adverse effects of most medicines. One of the main aims of clinical pharmacology is to understand the basis of this variability. Whether it is due to differences in drug disposition caused by variations in absorption, distribution, transport, metabolism, or elimination, or by differences in end-organ responsiveness, many studies have shown that genetic variability is a most important determinant of each of these.

In the field of drug discovery, the application of genetics was originally focused on the discovery of novel disease genes that could become the targets for new drug discovery programs. But the rapid expansion of understanding of the variability of human DNA sequences has given rise to an appreciation that this approach may be more challenging than originally thought. Currently, more use is made of population-based genetic association studies to identify disease intervention targets.

As the recent report of the Royal Society "Personalised Medicines: Hopes and Realities" makes abundantly clear, it is easy to exaggerate the importance of pharma-cogenetics on clinical practice. While there are a few medicines on the market where there is evidence for the benefits of genetic testing for patient selection, mainly in the field of cancer, there are as yet no marketed products that are the result of genetic-based discovery. It seems likely that this situation will radically change, but the time scale is not yet clear. It seems more likely that, for the foreseeable future, the impact of pharmacogenetics will be most profound in the development of diagnostic tests that will allow for the better use of medicines, both in terms of efficacy and safety.

This book is a timely account of the state of the science and clinical application of pharmacogenetics. Its format should make it attractive and easy to use for the clinician in search of detailed information about specific disease areas, and also for those wishing to be updated in the field of pharmacogenetics in general.

Alasdair Breckenridge Medicines and Healthcare Products Regulatory Agency

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