Around 15 years ago pharmacogenetics was predicted to revolutionize pharmacotherapy.
Patients would no longer be treated with standard drugs in a standard dosage. Instead,
the right drug in the right dose would be selected for each individual based on a
genetic test. Individuals likely to experience adverse events would be identified
prior to drug treatment, and personalized medicine would be within close reach. Unfortunately,
this prediction has not materialized. Although pharmacogenetic studies have found
correlations between pharmacokinetic parameters and gene polymorphisms for a large
number of drugs, very few physicians have ordered pharmacogenetic tests for their
patients outside clinical trials. Technical advances have outpaced clinical implementation.
The time needed to genotype, and the cost associated with these tests, have been reduced
to a level that is no longer prohibitive for widespread use. Not only detection of
single-nucleotide polymorphisms (SNPs), but also more extensive whole-genome sequencing
is now widely available.
The FDA has included pharmacogenetic information in the labels of more than 150 approved
drugs. To assist physicians, the Royal Dutch Association for the Advancement of Pharmacy
established a Pharmacogenetics Working Group that developed pharmacogenetics-based
therapeutic (dose) recommendations following a systematic review of the literature
[1]. In order to facilitate clinical application, the dose recommendations are now being
integrated into electronic prescription systems, with the assumption that this type
of clinical decision support will encourage physicians to use the available information
[2], [3]. In addition, these recommendations were integrated with the Pharmacogenomics Knowledge
Base for each investigated drug and can be found under the ‘Clinical PGx’ heading
[4].
Many factors influence the between-patient variability in drug response. Besides comorbidities,
interacting comedication and environmental factors the genetic variability is just
one of the factors that may influence the outcome of treatment. In pediatric patients
also the ontogeny in drug transporters and drug metabolizing enzymes need to be taken
into account. For the vast majority of drugs this contribution of pharmacogenetics
is below 20% and unlikely to lead to a useful pharmacogenetic test. Yet, there are
drugs for which the contribution of pharmacogenetics to overall variability is substantial,
and we should carefully consider implementing these tests into our daily practice.
In my presentation I will examine the evidence that pharmacogenetic information can
predict the pharmacokinetics or the pharmacodynamics. The potential impact of these
data on clinical practice will be discussed.
