Download Pharmacogenomics, Second Edition by Werner Kalow, Urs B. Meyer, Rachel F. Tyndale PDF

By Werner Kalow, Urs B. Meyer, Rachel F. Tyndale

Reflecting the shift from genetics to genomics within the pharmaceutical sphere, this moment variation strains the evolution of the technological know-how of pharmacogenetics and gathers study from the vanguard of the field-spanning the main influential breakthroughs in molecular diagnostics, metabonomics, proteomics, bioinformatics, illness mapping, pharmacodynamics, and illness gene id.

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Genes rarely act in isolation and hence, genetic contributions to pharmacological variability are subject to influences by gene–environment interactions as well as epistatic interactions among various genetic loci (49–51). Indeed, the most likely scenario is that the underlying basis of genetically determined variability in treatment response and common ADRs is polygenic. It is therefore often difficult to estimate the composite genetic component in pharmacological traits (27). This information is essential before decisions on further molecular pharmacogenomic work can be justified.

Interindividual variability in drug effects and the lack of reliable predictors of this variability are increasingly recognized as important barriers to science-based therapeutics (6–8). Moreover, the public health consequences of uncertainty in drug efficacy and safety have been increasingly documented by recent pharmacovigilance studies (9–13). A number of policy initiatives, particularly those on ADRs, further added to the momentum for personalized therapies in health care (10,14). Notably, present genetics-based efforts to individualize drug therapy have a more mechanistic focus in contrast to the previous empirical initiatives on personalized medicine using less precise demographic and descriptive clinical characteristics of the patients or the attendant disease (6,15,16).

Kalow W, Tang BK, Endrenyi L. Hypothesis: comparisons of inter- and intraindividual variations can substitute for twin studies in drug research. Pharmacogenetics 1998; 8:283–289. 39. Kalow W, Ozdemir V, Tang BK, Tothfalusi L, Endrenyi L. The science of pharmacological variability: an essay. Clin Pharmacol Ther 1999; 66: 445–447. 40. Ozdemir V, Kalow W, Tang BK, Paterson AD, Walker SE, Endrenyi L, Kashuba ADM. Evaluation of the genetic component of variability in CYP3A4 activity: a repeated drug administration (RDA) method.

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