In this Expert Review, John Hammond examines how genetic analysis can be useful in designing drug regimens. It outlines where the best gains for drug safety can be made and how genotyping can help form part of the solution.
The past decade has seen a rapid accumulation of data on the genetic content of the human cell. At the same time, fast and economic techniques for DNA analysis have been developed. As a consequence, we are now at a stage where genotype-drug interactions can be investigated relatively easily and the information used to reduce risk in drug therapy.
The proportion of individuals in the population who are sensitive to a drug by genotype, however, is small. This makes statistically significant data on drug sensitivity by genotype difficult to acquire, and means that validating the relationship is a challenge.
Yet the challenge is not insurmountable. Approaches exist through which it is possible to identify genes that regulate the hitherto unknown processes that modify drug response. By comparing the genetic profile of individuals who respond differently to a given drug with those of normal responders, identification becomes possible.
Use of genetic data and techniques also has the potential to assist the development of drugs against new and better-defined targets than those produced in the past, as well as influence how they are tested. Nevertheless, although knowledge of genetic influences on drug response is emerging as an important development for drug safety, there are some natural limits to its application. There is little sense in applying genotype testing to drugs for which there is already an adequate means of predicting dose outcome. Nor is it useful to determine genotype where there is no significant difference in drug response in vivo, even when alleles causing abnormal drug metabolism in vitro are present. Despite this, there are cases where genotyping has obvious benefits for safety.
Bioinformatics and Drug Safety assesses these benefits, outlining where the best gains for drug safety can be made and how genotyping can help form part of the solution.
CONTENTS
Introduction
About the author
Drug response variability
Genetic infl uence on drug response
The mechanism of inheritance
Using genotype to predict safe drug dosage
Multiple genes may influence safe drug dosage
Identifying genes involved in drug response
Population differences in allele frequency
Making use of pharmacogenetic data
Conclusions
References
Further reading
ABOUT THE AUTHOR
John Hammond graduated in Biochemistry and Soil Science from the University of Wales, following this with research for an MSc in the same subject. He was later awarded a DPhil in fungal biochemistry from the University of Sussex. He worked as a government research scientist at the Glasshouse Crops Research Institute, and then at Rothamsted Experimental Station for 17 years, working on fungal and plant biochemistry, molecular biology and genetic manipulation, and authoring over 40 research papers. He has also held visiting research fellowships at the University of California, King’s College, London and the University of Surrey.
After leaving full-time research he was appointed senior lecturer, and later reader, in molecular genetics at the North East Surrey College of Technology. In these positions he developed and taught courses on molecular genetics, biotechnology and DNA technology for undergraduate and postgraduate students. As well as continuing with part-time lecturing in medical and molecular genetics at the college, he now writes on molecular and genetic aspects of medicine, and constructs websites and online learning materials for healthcare companies, as principal of Bioupdates Consultants. He is a Member of the Institute of Biology and a Chartered Biologist.
Establishing the safest and most efficient drug regimen for a patient can be a trial-and-error process that can, in some cases, place patients at risk. Variability in response to certain drugs between different patients has major implications for the pharmaceutical and healthcare industries.
The ability to determine the correct drug and dosage for therapy at the outset would contribute significantly to drug safety. It would also lead to a more economical use of drugs, with potential savings for healthcare providers.
It is becoming clear that variability in drug response may be inherited. With the application of genetic analysis, DNA analytical techniques and pharmacokinetics, it has become possible to identify the genes, and the proteins which they encode, that are involved in drug responses.
This Expert Review, Bioinformatics and Drug Safety, looks at how to identify the genes involved in drug response, characterise the variants and devise a convenient means of identifying variants in a patient. It shows how genetic analysis can be a useful tool in designing the drug regimen for the best risk/benefit, and makes a case for genotype testing prior to prescription, and for genotype determination as a part of the clinical trial process.
KeywordPharma publications can be reprinted in bulk on demand. We will be pleased to discuss any branding requirements you have - for example you may wish to include company logos and advertorial. Likewise, individual e-documents can be licensed for multiple-user access, either on web sites or on company intranets. Please contact us.
