**Abstract**

Pharmacogenomics is defined as the study of genes and how an individual response is affected due to drugs. Pharmacogenomics is an emerging new branch with combination of both pharmacology (the branch of science that deals with study of drugs) as well as genomics (the branch of science that deals with study of genes) for development of effective doses and safe medications tailored according an individual patient genetic makeup. Human Genome Project is one of the crucial projects in which researchers are developing and learning relation in genes and its effect on the body's response to medications. Difference in genetic makeup provides difference in effectiveness of medication and in future to predict effectiveness of medication for an individual and to study existence of adverse drug reactions. Besides advancement in the field of science and technology till date pharmacogenomics hangs in infancy. There is limited use of pharmacogenomics, but still, novel approaches are under clinical trials. In near future, pharmacogenomics will enable development of tailor-made therapeutics for treating widespread health problems like neurodegenerative, cardiovascular disorders, HIV, cancer, asthma, etc.

**Keywords:** pharmacogenomics, genomics, proteomics, personalized medicines, tailored drugs

### **1. Pharmacogenomics: overview**

Due to variability existence among individuals against drug therapy response, it is a challenging task to predict the degree of effectiveness of a medication to a particular patient. As we know various clinical factors which are known to affect drug response, for example body size, age, sex, hepatic and renal function, and associated drug use (**Table 1**). Along with these clinical factors, some pharmacological factors also play a major role which includes differences in metabolism, drug distribution and drug directed proteins [2, 3]. Recently, major causes of interindividual differences are shown by variations in genes encoding cytochrome P450 (CYP) and other metabolizing enzymes in plasma concentrations of some drugs [4, 5].

Pharmacogenetics and pharmacogenomics can be used interchangeably. Though, Pharmacogenomics refers to the whole range of genes that are related to the determination of drug efficacy and safety whereas pharmacogenetics means monogenetic variants which alter the drug response [6, 7]. Pharmacogenomics is defined as study of genes and how they affect an individual response to the


#### **Table 1.**

*Genome-wide association studies in pharmacogenomics [1].*

administered drugs. Pharmacogenomics is emerging new branch with combination of both pharmacology (branch of science which deals with study of drugs) as well as genomics (the branch of science which deals with study of genes) for development of effective doses and safe medications tailored according an individual patient genetic makeup (**Figure 1**) [8, 9].

Basically, the concept for pharmacogenetics was left unknown for more than 50 years. This study underlined to the molecular mechanisms in account for their variation in responses to drug due to inherited characters and in drug development process. Pharmacogenomics applications can be employed in the improvement of discovery of new entities and its development with two possible ways: target the new drug targets or development of new entity to overcome drug resistance, and another way is to optimize the pharmacokinetics and metabolism of drug for reduction of the drug level variations [10]. In fact, personalized drug therapy or individualized drug therapy is not an easy task. It needs many folds as there may be a lack of information regarding drug action, genomic elements of important disease pathogenesis, especially for complex diseases. Also, large scale clinical studies are sometimes becoming a big challenge for the researchers [11]. The correlation of pharmacogenomics and cancer would expand the specific anticancer drugs with better chemotherapeutic outcomes [12–15]. There are prominent examples with recent clinical and pharmaceutical restrains where the molecular based mechanisms are involved in various drug responses were observed among the patients and diagnosed with the similar diseases [16, 17]. Moreover, various polymorphisms existence at genetic levels in genes found to have association with alteration in responses of drug and rate of ADRs in humans (**Table 2**) [18].

Finally, pharmacogenomics-based development of drug and its regulation will open the doors for new as well as targeted drug development for promoting safe, effective, and cost-effective drug therapy for individual. The theoretical origin for pharmacogenomics is outlined by Sir Archibald Garrod's in book entitled as "1939 Inborn Factors of Disease" [19].

Pharmacogenetics is the study of how an individual person's genes respond to a drug. This branch is associated with genomics is genetic level studies with functional studies and pharmacology (includes pharmacokinetics and pharmacodynamics). All these branches together aid in the development of safe, and effective medications along with doses which are probably tailored to an individual persona genetic makeup [20–24]. Pharmacogenetics is indicated as major clinically proven

**17**

**Figure 1.**

*Pharmacogenomics: Overview, Applications, and Recent Developments*

application in terms of advancement in human genomic science. This potentiates a revolution in drug therapy. As a result, diseases which range from depression to viral infection and from childhood leukemia to hypertension are treated or controlled for enhancing the quality of life of patient. Most medicines at present are available as "one medication fits all" but they sometimes were not capable to work same to everyone. So, it is difficult to envisage who will have benefit result and who will have negative side effects. Also, the knowledge which scientist have acquired due to extensive work on Human Genome Project and are learning about inherited variations of genes and there effect on body's response to medications. Conditions in which responses of an individual to certain drugs include Stevens-Johnson syndrome or epidermal toxic necrolysis, clopidogrel resistance, malignant hyperthermia, warfarin sensitivity and its resistance and thiopurine S-methyltransferase deficiency [25].

**Polymorphic gene Drug Effect** CYP2C9 Phenytoin Toxicity

Human leukocyte antigens (HLA) Abacavir Related to

Isoniazid

CYP2D6 Codeine Toxicity

MDRI Antiepileptic drugs Drug response

TPMT Anticancer drugs like 6-thiopurine,

N-acetyltransferase (NATs) Sulphonamides, hydralazine,

Warfarin Bleeding risk Glipizide Hypoglycaemia

Irinotecan Toxicity

Fluoxetine Toxicity

Toxicity

Toxicity, hypersensitivity

hypersensitivity

6-Mercaptopurine, azathioprine

*DOI: http://dx.doi.org/10.5772/intechopen.93737*

*Development of pharmacogenomics and pharmacogenetics.*

UDP-glucuronosyltransferase 1A1

*Genes with altered drug response.*

(UGT1A1)

**Table 2.**

*Pharmacogenomics: Overview, Applications, and Recent Developments DOI: http://dx.doi.org/10.5772/intechopen.93737*

#### **Figure 1.**

*Drug Design - Novel Advances in the Omics Field and Applications*

**Factors Effects**

Targets of ADRs Drug toxicity Drug transporters Drug disposition

a. **Genetic factors**

b. **Environmental factors**

c. **Physiological factors**

starvation

**Table 1.**

Environmental chemicals, alcohol drinking, combined drugs effect, and dietary substances

Age, sex, pregnancy, exercise, disease state,

*Genome-wide association studies in pharmacogenomics [1].*

patient genetic makeup (**Figure 1**) [8, 9].

administered drugs. Pharmacogenomics is emerging new branch with combination of both pharmacology (branch of science which deals with study of drugs) as well as genomics (the branch of science which deals with study of genes) for development of effective doses and safe medications tailored according an individual

Drug efficacy, toxicity, and pharmacokinetics

Drug efficacy, toxicity, and pharmacokinetics

Drug-metabolizing enzymes Drug metabolism (pharmacokinetics) Therapeutic targets Drug efficacy (pharmacodynamics)

Basically, the concept for pharmacogenetics was left unknown for more than 50 years. This study underlined to the molecular mechanisms in account for their variation in responses to drug due to inherited characters and in drug development process. Pharmacogenomics applications can be employed in the improvement of discovery of new entities and its development with two possible ways: target the new drug targets or development of new entity to overcome drug resistance, and another way is to optimize the pharmacokinetics and metabolism of drug for reduction of the drug level variations [10]. In fact, personalized drug therapy or individualized drug therapy is not an easy task. It needs many folds as there may be a lack of information regarding drug action, genomic elements of important disease pathogenesis, especially for complex diseases. Also, large scale clinical studies are sometimes becoming a big challenge for the researchers [11]. The correlation of pharmacogenomics and cancer would expand the specific anticancer drugs with better chemotherapeutic outcomes [12–15]. There are prominent examples with recent clinical and pharmaceutical restrains where the molecular based mechanisms are involved in various drug responses were observed among the patients and diagnosed with the similar diseases [16, 17]. Moreover, various polymorphisms existence at genetic levels in genes found to have association with alteration in

Finally, pharmacogenomics-based development of drug and its regulation will open the doors for new as well as targeted drug development for promoting safe, effective, and cost-effective drug therapy for individual. The theoretical origin for pharmacogenomics is outlined by Sir Archibald Garrod's in book entitled as "1939

Pharmacogenetics is the study of how an individual person's genes respond to a drug. This branch is associated with genomics is genetic level studies with functional studies and pharmacology (includes pharmacokinetics and pharmacodynamics). All these branches together aid in the development of safe, and effective medications along with doses which are probably tailored to an individual persona genetic makeup [20–24]. Pharmacogenetics is indicated as major clinically proven

responses of drug and rate of ADRs in humans (**Table 2**) [18].

Inborn Factors of Disease" [19].

**16**

*Development of pharmacogenomics and pharmacogenetics.*


#### **Table 2.**

*Genes with altered drug response.*

application in terms of advancement in human genomic science. This potentiates a revolution in drug therapy. As a result, diseases which range from depression to viral infection and from childhood leukemia to hypertension are treated or controlled for enhancing the quality of life of patient. Most medicines at present are available as "one medication fits all" but they sometimes were not capable to work same to everyone. So, it is difficult to envisage who will have benefit result and who will have negative side effects. Also, the knowledge which scientist have acquired due to extensive work on Human Genome Project and are learning about inherited variations of genes and there effect on body's response to medications. Conditions in which responses of an individual to certain drugs include Stevens-Johnson syndrome or epidermal toxic necrolysis, clopidogrel resistance, malignant hyperthermia, warfarin sensitivity and its resistance and thiopurine S-methyltransferase deficiency [25].
