The Implementation Of Pharmacogenetics Biology Essay

Published: Last Edited:

This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.

Pharmacogenetics is the study of how individual's genetic makeup affects responses of the body to drugs. The term pharmacogenetics was first used in 1959 to describe a new discipline based on the observation that genetic factors, at that time variation in the function of a single gene, can modify drug action.[a] Although pharmacogenetics has been existence for nearly half a decade, the development of it is rather slow until the completion of the Human Genome Project (HGP) coordinated by the U.S. Department of Energy and the National Institutes of Health[b] which is one of the greatest scientific breakthrough for the past 50 years. The project identified thousands of protein-coding genes in the human genome and sequenced the billions of chemical base pairs that make up human DNA.

A gene is a strand of DNA which is made out of sequences of nucleotides in coding regions and non-coding regions. The sequence of nucleotides in a coding region denotes the amino acid sequence of a protein that will make the cell function. Variation in one of the nucleotides "letters" A, T, C or G in the coding region, known as single nucleotide polymorphisms (SNPs)[c] will have a significant effect on how an individual develops disease or responds to a drug as the denoted amino acid sequence will alter the protein produced in cells.

The study of human genetics will speed up the development of pharmacogenetics as the genetic information obtained can be use to inform prescribing decisions and allow more accurate prediction of drug safety and efficacy in individual patients. Application of pharmacogenetics mainly fall into two fields, that is, the use of genetic information to test for variation in the individual DNA which will affect the patient's response to drug by, for example, different level of drug metabolising enzyme in the body. Pharmacogenetics also can be used to analyse the DNA of tumour cells which is different from human genes and allow the use of drugs that target that specific gene.

The study field of pharmacogenetics will eventually lead to tailor-made drugs adapted to each individual's genetic make-up. It will surely have many benefits in improving human's health. However, the field is still in infancy and will also have barriers in its implementation in pharmacy practice.

Pharmacogenetics Test

Pharmacogenetics test is the assay of an individual genetic to detect the variation, or single nucleotide polymorphism in the genetic code in order to predict their responses to drug. The genetic variation will determine the efficacy of a drug or the likelihood to sustain adverse drug reaction by the patient. The test can be done by direct analysis of the patient's DNA or indirect analysis of the DNA influenced molecules, like RNA or proteins. Pharmacogenetics test can be done on blood samples, cheek swabs or in cancers biopsy tissue.

Potential Benefits of Pharmacogenetics

Being an important breakthrough in healthcare industries, pharmacogenetics will have potential benefits in drug manufacturing. First of all, more powerful medicines can be designed through pharmacogenetics. Drugs may be developed to target a specific binding site of cell which will maximise the therapeutic effects but decrease the damage to the nearby healthy cells. Through pharmacogenetics test, doctors can determine the drug that can be used according to the genetic profile of a patient and thus reducing the likelihood of adverse drug reactions (ADRs). The accurate dosage of the drug to be used can also be determined based on the individual's genetics instead of body weight and age. Vaccines also can be produced from genetics material which will have all the benefits of existing vaccines but with reduced risks of infections.

Drug Development

For a medicine to be available in the market, massive research and clinical trials need to be done before the drug can be developed. Table 1 shows the phases of clinical development of a drug. This is an expensive and time consuming process. It is shown statistically that for a drug to be launch into the market, the duration that is needed is approximately 13 to 14 years while the financial investment can goes up to as high as US$1 billion.[d] Even with such investment, most projects tend to fail and eventually lead to unsuccessful development of new medicine. With the involvement of developing pharmacogenetics, the success rate of a drug to be developed will be much higher.

Table 1 Phases of clinical development[e]

Phase I trials

These comprise the first exposure of humans to a putative medicine and are intended to explore pharmacokinetic parameters and ensure that there are no grossly unacceptable safety or tolerability issues. Typically up to 100 individuals may take part in a series of studies aimed at generating information on pharmacokinetic parameters such as bioavailability, the rate and route of clearance and any signs of drug-drug interactions.

Phase II trials

These are conducted in patients and look to establish an initial indication that the compound is effective. The studies (which may involve up to 1000 individuals) are sufficiently large that some safety signals may be apparent, especially so-called 'nuisance' or quality of life (QOL) side effects such as reversible changes to liver function tests. Establishing key efficacy (and safety) parameters is a crucial part of the phase II studies

Phase III trials

These large trials, costing tens or even hundreds of millions of pounds, provide the most convincing evidence of efficacy and safety to support a regulatory submission. To minimize bias and variability, they are usually randomized controlled trials (RCT). For example, the double-blind RCT model, where neither the physician nor the research subjects know which arm of the study (active drug or placebo/standard care) the patient is assigned to, is the phase III 'gold standard'. Owing to the size of these studies, less common adverse events may become apparent.

Phase IV trials

Once a medicine is registered, it can be used by a much wider population of patients. At this stage (phase IV), rare adverse events may be identified that could not be discovered during clinical development: even the large pivotal phase III studies lack the power to detect adverse events occurring at rates less than 0.1%.

With the knowledge of genetics, pharmacogenetics allows us to understand the underlying principle of how human body reacts to a drug and thus reducing attrition in pharmaceutical research. There are two ways to apply pharmacogenetics in drug development. By retrospective method, insights on a drug kinetic and dynamic properties, effectiveness and also adverse drug reaction can be observed from past results of clinical trials using genotype data. Prospectively, patient's subgroups that will have a positive or negative response to a medication can be identified through genetic information. All this data will help to reduce the time frame for phase III trials and increase the chance to succeed if they were obtained during phase II.

By exploring gene variation that affects pharmacokinetics, especially drug metabolising enzymes, dosage selecting of a drug for different genome population can be determined more accurately instead of just based on phenotype variants. For example, variation in the level of CYP2D6 enzyme due to gene factor will affect one's requirement for the dosage of some pain relieving drugs such as codeine.[f] Individual with lower level of the enzyme will require a lower dosage while those with higher level of the enzyme will require a higher dosage to achieve the same effect. Drugs efficiency may vary due to different genetic makeup and pharmacogenetics can be used to predict the drug's efficacy. After identifying the appropriate responding patient subgroups during clinical trials, compounds that are only effective specifically can still be developed further for the treatment of a population, unlikely previously where a project will be terminated if the drug seems to be less effective cases during clinical trials.

During development of a medicine, the safety of the medicine is yet to be determined. However, any negative occurrence during the clinical trial, especially phase II, will significantly affect the further development of the drug. By undertaking pre-genetic screening, high risk patients can be identified and excluded from the clinical trials. This will increase the overall safety of the drug and thus ensure further research of it. Besides, by identifying the genetic that will have a negative response to a drug, manufacturer can include the information in the drug description leaflet. Doctors will be aware of the information and perform pharmacogenetics test for patients before prescribing. This will in turn reduce the probability of adverse drug reaction which can be fatal in certain cases.

Roles of Pharmacists

Currently, only a small amount of pharmacists that are involved in pharmacogenetics, particularly those who are specialist like in the field of HIV service or oncology. The increase involvement of pharmacists in clinical areas will eventually expose pharmacists to pharmacogenetics. Pharmacists will need to, for example, interpret the test result from pharmacogenetic test and determine the appropriateness of the drug prescribed. In the same time, pharmacists will be counselling patients about the implication of the result and advice them on medication intake base on the result. Last but not least, pharmacists can keep the pharmacogenetics test result together with the patient's medical record for future referencing while monitoring and reviewing the treatment.


While there are hopes that pharmacogenetics will eventually lead to tailor made drugs, we must bear in mind that one's responses to drug can be due to environment factor and others, not solely genetic makeup. Furthermore, current advancement of pharmacogenetics that are mainly based on single nucleotide polymorphism will not be sufficient as most of the common disease in aging like heart failure, hypertension are more likely to be multigenic based. Pharmacists will not be ready for the implementation of it if they do not acquire relevant knowledge about human genetics. They will need to access to appropriate education regarding pharmacogenetics to keep pace with the ongoing development and prepare for its implementation in near future that will revolutionise healthcare industry.