How to Cite:

Alsuwaileh, A. N., Albakheet, I. A. I., Aljaloud, H. A., Aljadeedi, A. K., Alyami, S. H., &
Alrashed, A. H. M. (2024). The role of pharmacogenomics in personalized medicine: A
focus on drug metabolism. International Journal of Health Sciences, 8(S1), 1844–1859.
https://doi.org/10.53730/ijhs.v8nS1.15423

The role of pharmacogenomics in personalized

medicine: A focus on drug metabolism

Ali Nasser Alsuwaileh

KSA, National Guard Health Affairs

Ibrahim Abdulaziz Ibrahim Albakheet

Albakheet- Public Health

Hammad Abdullah Aljaloud

KSA, National Guard Health Affairs

Abdullah Khalifah Aljadeedi

KSA, National Guard Health Affairs

Saeed Hassan Alyami

KSA, National Guard Health Affairs

Abdulaziz Hussain Mohammed Alrashed

National Guard Health Affairs

Abstract---Background: The conventional model of drug treatment

may involve set protocols of drug use and not the currently variegated
pharmacology patterns due to mutations in drug metabolism
enzymes. But recent innovations in pharmacogenomics have provided
new insight on feeds and processing of drugs through genetic and
environment components that present a more divergent view of
treatment. Aim: The purpose of this study is to understand drug
metabolism specificity in the framework of individualized medicine
and its potential to enhance the efficacy and safety of a drug due to
genetic and lifestyle differences. Methods: A literature search was
performed to compare the effects of genetic variations and
environment as to drug metabolism. The research also focuses at how
the pharmacogenomics testing is used in developing the custom drug
therapies. Results: major impact in the rate of metabolism of drugs
along with their effectiveness and toxicity. Of course, assessing
health-promoting behaviours that include diet and physical activity,
or the lack of thereof, as well as others, can strongly impact
therapeutic success. Conclusion: Potential for manufactured Meal is

International Journal of Health Sciences E-ISSN 2550-696X © 2024.

Corresponding email: [email protected]
Manuscript submitted: 01 Jan 2024, Manuscript revised: 09 Jan 2024, Accepted for publication: 15 Jan 2024
1844
 1845

its ability to highlight the vests in drug metabolism that are crucial for
finding personalized treatments. Through the use of
pharmacogenomics testing in medical practice, recommenders can
enhance safety and effectiveness indicating a better patient outcome.

Keywords---Pharmacokinetics, pharmacogenomics, gene-

pharmacotherapy, genetic differences, side effects of drugs,
pharmacogenomics analysis.

Introduction

Pharmacological field has tended to practice the treatment based on the principle
that one size fits all, where most patients receive the same medications and
doses. Nevertheless, recent research in pharmacogenomics dictated considerable
importance to the drug metabolism variation to the general outcomes of the
therapies. Pharmacokinetics, the rate and manner that the body handles
medications, are different across users. The pharmacogenomics model suggests
that there are genetic variations, which were coupled with other factors like diet,
and lifestyle and age to explain the way in which individuals metabolize drugs.
These variabilities can hence result in variation in the effectiveness and toxicity of
the drugs which makes it important to embrace personalized medicine. By
understanding the factors that cause variation in drug metabolism genes and
environment, a doctor is in a good position to recommend a drug of most
appropriate efficacy and least side effect in a gentleman. This paper aims at
examining the idea of drug metabolism interpersonal difference and the
importance of these discoveries for the contemporary generation of individualized
medicine approaches. [1,2]

An explanation of what genetic differences are and how they affect the
metabolism of a drug

Polymorphisms drug metabolism Polymorphisms are variations in genes within

individuals and are said to be critical in providing information on how a certain
medicine can or cannot be metabolized in the body. These differences exist in the
genes of enzymes, transporters, and receptors located in the biopharmaceuticals’
absorption, distribution, metabolism, and excretion (ADME) system. Of these, the
largest body of work has been dedicated to the cytochrome P450 (CYP) enzyme
family, which metabolizes over 70 percent of the drugs in clinical use.
Polymorphisms exist in CYPs like CYP2D6, CYP2C9, and CYP2C19 therefore
putting patients into categories with poor metabolism, intermediate metabolism,
normal metabolism, and ultra rapid metabolism. For example, a man with a
nonfunctional CYP2D6 gene may get little benefit or high toxicity of drugs such as
codeine or tamoxifen and a woman with the ultra-rapid CYP2D6 gene may clear
the drug from her system before it can be effective.[3,4] The variations in the gene
therefore have even wider implications that affect drug transporters for instance
P-glycoprotein encoded by the ABCB1 gene and receptors including the vitamin K
epoxide reductase complex (VKORC1). Polymorphisms in ABCB1 can actually
affect the absorption and distribution of drugs such as digoxin or anti-cancer
agents. Likewise, genetic variability identified in the gene encoding vitamin K
1846

epoxide reductase complex subunit 1 (VKORC1) can have a direct impact on the
sensitivity of patients to warfarin and as a result must involve dose titration
based on genotyping. [5] These genetic differences explain why the
pharmacogenomics tests are important as they help clinicians determine how a
patient will metabolize the drugs, which drug reactions the patient is likely to
have, and which drugs will work best in treating illness.[6]

Moreover, multiple gene and environment interactions complicate drug

metabolism which poses a challenge when prescribing drugs. For instance, people
with genetic polymorphism may need to readjust the drug metabolism because of
interactions with other drugs, food products or exacerbating pathologic
conditions. This showcases why it takes more than pharmacogenomics data to
adapt it to clinical and lifestyle data for an individual patient. The study goes on
and new variants are identified over time which make the scope of the impact of
genetic profiles in drug metabolism even broader, opening the door for better and
more tailored approaches to health care.[7]

Pharmacogenomics: Tools for Optimizing Therapeutic Benefits

Pharmacogenomics is a flagship model of personalized medicines and

encompasses a unique concept of targeting treatment outcomes to the genetic
makeup of an individual. Genetic differences play a very important role in
understanding how different patients respond to different drugs in terms of
metabolism, therapeutic effects and toxic effects. The molecular information
derived from pharmacogenomics studies thus provides the healthcare
professionals the opportunity to shift from this one size fits all mentality to a
much more strategic approach that ensures, on the one hand, the maximal
therapeutic effects of the drugs and on the other reduces the probability of side
effects as much as possible. For example, pharmacogenomics studies can be used
to determine genetic factors that determine which patients will likely benefit from
use of a certain drug and which patients will need a different dosage schedule.
This is more relevant especially in handling complicated illnesses such as cancer,
cardiovascular diseases, and mental health illnesses in that drug impacts differ
from one client to another. [8,9]

Pharmacogenomics in practice can be illustrated trough the most representative

example of the targeted therapies, which are applied for cancer. This is because
drugs such as trastuzumab for HER2 positive breast cancer are only given to
patients with HER2 receptor positive tumors. Likewise, pharmacogenomics has
revolutionized the handling of therapeutic with narrow margins of safety such as
the use of warfarin. CYP2C9 and VKORC1 pharmacokinetic testing helps the
clinician identify the right starting dose and so helps avoid bleeding or
thromboembolic events. This approach does not only enhance the safety of
patients but also shortens the process that takes when administering an
appropriate drug and its correct dosage .In addition to the issue of treatment
effectiveness, pharmacogenomics is crucial in stopping serious ADRs, which
remains one of the major causes of morbidity and mortality. Genetic testing can
identify patients at risk of severe ADRs, such as hypersensitivity reactions to
carbamazepine or batcaver, by detecting HLA-B15:02 and HLA-B57:01 alleles
respectively. Clinicians’ decisions to avoid specific drugs that are potentially
 1847

dangerous will reduce adverse effects and increase patient compliance or therapy.
In addition, the application of pharmacogenomics in prescribing leads to the
decrease in the healthcare spending on hospitalizations and treatment of
condition that arises from side effects of drugs. [10]

While the indications of how to ensure maximum effectiveness of an administered

drug are still being explored, there is a sense that pharmacogenomics research is
opening up new possibilities. Multiple genetic variant or polygenic risk scores are
more effective in assessing drug responses than single genetic variant.
Pharmacogenomics implementation within EHRs also enhances clinical decision
support in real-time through delivery of personalized interventions at the point
care. That is why ongoing improvements make pharmacogenomics more available
than before; though some challenges still persist for example high costs of genetic
tests and the need to develop stringent clinical reference levels. Lastly, there are
expectations of advancement of pharmacogenomics within routine prescribing in
regards to ‘personalized medicine’ and improved health care. [11]

Linking Human Genomics and therapeutics for Personalized Medicine

Genetics brought into the practice of medicine new paradigms for constructing
individualized approaches to treatment, establishing the new epoch in medical
practice. It is referred to as precision or personalized medicine, wherein the ability
of an individual to respond to certain medications, features of disease and
therapeutic effects are first forecasted based on their genetic structure.
Translating genetics to medicine extends the current medical practice by allowing
clinicians envision a diagnostic and therapeutic approach that interfaces with an
individual’s biology. This shift in paradigm also directly translates to reduction of
adverse effects due to wrong or non responsive treatments.[12] An Important area
where genetics come in handy is in pharmacogenomics, in terms of how gene
differences manifest themselves in terms of drug response. Pharmacogenomics
can show if a patient is a non-responders or has moderate or highly rapid rate of
metabolism to some drugs including antidepressants, pain relievers,
chemotherapy drugs, among others. For instance, patients with CYP2C19
variations may need different dosing or even different medication when using
products like clopidogrel a blood thinner used to prevent heart attacks and other
cardiovascular complications. Likewise, oncology treatment has advanced
remarkably with genetic testing which includes the therapeutic agents like
Imagine to chronic myeloid leukemia or summertime in EGFR mutated lung
cancer because this technique is targeted and cost-effective, less hazardous have
a higher potential for cure.[12]

Besides, drug response, genetic information will be useful in proactive diagnosis

of diseases to which one is most likely to be prone. For example, people with
BRCA1 or BRCA2 genes can get information of screening and early preventing
plan of breast and ovarian cancer. In addition, with today’s powerful technologies
such as whole-genom and exom sequencing, clinicians are able to look for rare
genetic diseases or multiple genetic predisposing factors towards common
diseases to improve the diagnostic precision and treatment planning. [13] Main
issues of genetic integration into medicine include multidisciplinary cooperation
as well as organization. Physicians, genetic counselors and pharmacologists as
1848

well as bioinformaticians coordinate the interpretation and application of genetic

data in clinical practice. This relationship guarantees that we capture the unique
features of images meaning that genetic information is well explained, and
informed choice is made, and patients well educated. Furthermore, genetic data
can now be integrated into the treatment Iter process with the help of newly
developed digital tools and electronic health records (EHRs) .Still some of the issue
persist which are, cost of the genetic testing, ethical issues and inequality in
genetic based treatments and diagnosis. To address these barriers, more funding,
education, and focused policy to advance these goals for the elimination of
barriers to genetic services are needed. Lastly, the connection between genetics
and medicine is about the future of medicine and how disease can be diagnosed,
treated and prevented, in other words how medicine can be tailored and made
precise.[13]

Pharmacogenomics And Its Role in the Development of Precision Medicine

Pharmacogenomics is an important part of the precision medicine since it allows

adapting the required therapy depending on a patient’s genes. This is quite
different from the usual treatment, which starts with treatment modalities
formulated with treatments that cater for the average patient without considering
their genetics and the rate at which their body will metabolize
pharmacogenomics. This framework guarantees that clients get the correct drug
in the correct amount, aiming at reducing effective drug reactions and boosting
valuable therapeutic total results. Pharmacogenomics is a direct combination of
genetic science and clinical practice which has revolutionized disease
management and treatment to a patient-oriented model. The best example of
pharmacogenomics contribution to precision medicine involves the genetic
variation that affects drug metabolism. For instance, the cytochrome P450 (CYP)
enzyme family is well known to be involved basically with the metabolic process of
most drugs. Polymorphisms in CYP genes including: CYP2D6, CYP2C9 and
CYP2C19 affect the activity of these enzymes and thus bring about considerable
genetic difference in drug metabolism. For instance, patients who have genetic
variations in CYP2D6 metabolize antidepressants or opioids too rapidly or too
slowly, affecting drug effectiveness or generating toxicity. The pharmacogenomics
testing can help clinicians to modify medication therapy based on the results
allowing for the best therapeutic effects with the lowest risk possible.[14]

In oncology, pharmacogenomics has played a critical role in the development of

target therapies which is a signature of precision medicine. Pharmacogenomics
has made significant advances in cancer treatment, peripheral examples include;
trastuzumab which is used in treating HER2 positive breast cancer or imatinib
which targets chronic myeloid leukemia with specific gene mutations. Such
therapies are prescribed depending on the presence of genetic markers implying
that the therapies will work for patients who possess the right molecular
signature. Furthermore, pharmacogenomics information is being used in the
solution of drug resistance, one of the major problems in the treatment of cancer
by pointing out new routes or suggesting an appropriate set of drugs according to
the patient’s genes.[15] Pharmacogenomics also supports precision medicine
regarding lowering ADR rates, one of the prime causes of readmissions and costs.
Genetic testing for variants in HLA genes, such as HLA-B57:For example,
 1849

knowing from which gene, such as HLA-B*01 or HLA-B15:02, individuals are at

risk from hypersensitivity reactions to drugs such as batcaver or carbamazepine,
enables doctors not to prescribe it to at-risk individuals. It also increases patient
safety and strict compliance with adherent regimes as the risk of side effects are
minimized. Furthermore, pharmacogenomics is pivotal in the control of chronic
illnesses that demand extended drug treatment. For diseases such as
hypertension or diabetes, diagnoses of psychiatric disorders, or many others,
genetic testing assists in determining the best drug to use and the correct dosage,
NOT involving a process taking much time given that the patient’s lives will be
improved In the process. For instance, polymorphisms in SLCO1B1 which reflects
statin metabolism, can inform management of lipid profile and avoid statin
induced myopathy.[15]

While pharmacogenomics is an emerging discipline, data in EHRs and new

developments in genomic technologies are promoting precision medicine.
Additional work to establish pharmacogenomics databases and protocols also add
to simplification of its use in daily practice. However, issues including costs,
availability and the issue of awareness and knowledge among most of the
practitioners and patients present some of the major issues that hinder the
enough embracing of the innovation. Solving these problems is crucial to
optimizing the use of pharmacogenomics in changing the healthcare process.[16]
In conclusion, pharmacogenomics may be viewed as the best primary example of
the concept of precision medicine that suggests the scientific approach to
individualized pharmacotherapy. Thus, the population of patients receiving
appropriate drug treatment, as well as the genetic variability of the effectiveness
of medication, opens the door to the future in which medical treatment will be
carried out based on the genetic characteristics of the body. It not only ensures
improved clients’ throughputs or improved condition from the disease but also
work to ensure that the global health systems are made more efficient and
sustainable.

Personalized Drug Therapy: The Pharmacogenomics Approach

According to the principles of pharmacogenomics, the concept of individualized

drug treatment is clearly on the forefront of the new millennium trends. This
approach involves using the information about the person’s genetically
determined metabolism of a specific drug in order to prescribe the best dose and
sort of drug. Different from conventional treatment approaches, which mostly
involve the prescription of drugs in an empirical fashion, this forecasted model of
pharmacogenomics entails genetic profiling to determine a particular patient’s
capability to metabolize particular medication. This not only improves the quality
of operations and procedures, but also minimizes the likelihood of side effects and
diminishes the amount of useless treatments most importantly it minimizes the
cost of healthcare.[17] Pharmacogenomics is the scientific discipline which
supports an individualized approach to treatment through examination of genetic
factors that affect drug metabolism. For instance, the polymorphic genes
CYP2C19 which involve the metabolism of clopidogrel, an antiplatelet drugs used
for prevention of cardiovascular events. Reduced-function variants in patients
may fail to activate the drug as required hence making it to be less effective and
thus exposed to bad results. Such genetic differences are ascertainable through
1850

testing; the clinician can then recommend a different drug or even a different
dosage so that the patient can get the best form of treatment. Likewise, genetic
mutations in the TPMT gene affect the ability to metabolize thiopurine drugs that
are used to treat leukemia and autoimmune disease. Getting tested for these
variants means having the right dose with measures that can prevent toxicity that
may be lethal.[18]

The pharmacogenomics approach also applies to treatment of side effects and

ways of minimizing ADRs. Major gene variations for drug hypersensitivity are the
HLA-B alleles, for example, batcaver or carbamazepine. Measuring these markers
prior to commencing such therapy prevents adverse reactions that might be life-
threatening and enhances patient outcomes. The paradigm of
pharmacogenomics-guided therapies in oncology, such as HER2-positive breast
cancer and BRAF gene mutation melanomas treated with trastuzumab and
vemurafenib respectively, show how on the basis of genetic data therapies may be
selected resulting in enhanced survival. Furthermore, the pharmacogenomics
concept contributes positively to the treatment of chronic illnesses that require
extended drug therapies. For example, testing for SLCO1B1 variants in patients
taking statins to diagnose patients with predisposition to statin-induced
myopathy facilitates prescriber selection of safer drug options. Likewise, genetic
testing of CYP2D6 and CYP2C19 polymorphisms guides the appropriate choice of
antidepressant and dosage in psychiatric disorders and saves time required for
clinical improvement.[19] Pharmacogenomics in the application of personalized
drug action in also enhances patient oriented care. Patients want to be involved in
their treatment process, and by giving patients genetic information, clinicians can
build trust with them and ensure that the patient will follow the plan. Further,
pharmacogenomics information can be integrated into EHR and provide decision
support tools to later apply individualized approach to chronic patient care, as
well as, providing efficient communication between healthcare professionals.[20]

However, there is more evidence demonstrating the effectiveness of the

pharmacogenomics-based personalized therapy approach, yet multiple barriers
remain: the cost of genetic testing, provider knowledge about pharmacogenomics,
and unequal access to genetic services. But constant emergence in new Genomic
technologies and the work being done towards creating protocols for its
implementation is making pharmacogenomics accessible. Over time and with
increasing research, most pharmacogenomics biomarkers will be further
established and involve more patients in personalized drug therapy.[21] In its
turn, the approach based on pharmacogenomics of individuals defines the idea of
the right drug therapy for each person and reflects the further development of
medicines. When issues of genomics are combined with the provision of
healthcare to the patients, medical practice is made safer, more effective and
focused on the individual patient making the whole idea set to revolutionize
healthcare and enhance health status all across the world.

Researching Gene Factors Affecting Drug Response and Toxicity

Pharmacogenomics has developed into a focus of studying in order to determine

the genetic basis of drug response efficacy and toxicity. This [it stands to reason
that] genetic polymorphisms affect the pharmacokinetics of drugs as well as the
 1851

effect, effectiveness and toxicity associated with different drugs, resulting in

variations in therapeutic outcomes and ADRs. These differences are frequently
due to single base pair differences known as single nucleotide polymorphisms
(SNPs) in genes that code for drug-metabolizing enzymes, transporters and
receptors and are the basis for the prediction of individual drug responses. In this
way, the genetic options can help researchers and clinicians to perfect the therapy
plans, by having access to treatments that will be both effective for the patient
and not cause any harm.[22] One of the important ways that genetics brings
differences in drug metabolism is through difference in drug metabolizing
enzymes especially in the Cyp450 family. For instance, CYP2D6_A_ can make a
human being act as a poor metabolizer, intermediate metabolizer, extensive
metabolizer, or ultra-rapid metabolizer. Such differences affect drug-metabolizing
enzymes such as antidepressants, beta-blockers, and opioids. Patients who
metabolize a drug slowly may be exposed to toxic levels of a drug or substance
thus developing side effects while those who metabolize the same drug rapidly
may clear the drug or substance faster hence it may not have any effective
therapeutic effect. The same holds true for the other enzymes including CYP2C19
involved in the metabolic reaction of clopidogrel, which is an antiplatelet drug.[22]
Drug transporters through which drugs enter and exit cells are another important
focus of genetics with regard to drug pharmacokinetics. Polymorphisms in the
SLCO1B1 gene that codes for the OATP1B1 transporter influence the kinetics of
statin uptake in the liver. Statin use increases the occurrence of myopathy more
in patients with reduced-function variants hence recommending genetic test
before beginning a course on statins. Further, apparently genetic variations in
ABCB1 gene coding for P-glycoprotein may influence the distribution and
metabolism of drugs, the effectiveness of their treatment of diseases like cancer
and epilepsy.

SNPs also affect drug targets-receptors and enzymes on which a drug acts and
through which it produces its effect. For example, EGFR gene biomarkers define
whether tyrosine kinase inhibitors are effective for treating non-small cell lung
cancer. Likewise, polymorphic dialects of the target of warfarin, the VKORC1
gene, make variation difference in sensitivity to warfarin that calls for dose
refinement to avoid bleeding and clotting. The above cases are good examples of
how genetics also define not only pharmacokinetics but also pharmacodynamics
of drugs.[23] An important issue that is considered in medical practice – this is an
adverse drug reaction, of which genetic aspects are traditionally associated. Rare
alleles including types like HLA-B are also implicated to cause severe
hypersensitivity reactions. For example, HLA-B57:01 is associated with batcaver
hypersensitivity and HLA-B15:02 alleles are found in severe cutaneous reactions
to carbamazepine. The two genetic markers are discerned through testing so that
the clinician can avoid administering the high risk drugs to clients with the
inherent susceptibility, hence enhancing the safety of the patients.[24]
Investigating the role of genes in drug effectiveness and risks also relates with
large health concerns. By genetic analysis of population subgroups, progression
to therapies tailored for ethnicity and region could be made due to the concerns
with the drug-screen behaviorism variations. For instance, there are increased
prevalence of specific polymorphisms, CYP2C9 and VKORC1 in some populations
to the influence warfarin metabolism. The findings described in the contributed
papers can inform precise interventions targeting nuanced patient groups. [25]
1852

Although the analysis of genetic factors that control drug response has advanced
considerably, there are obstacles to that progress. The expensive rate of genetic
tests, relative rarity of doctor’s and patients’ knowledge of the tests, and the
difficulty of reading the results are among the JMHS’s issues. However genetic
cases are just one side of the coin while the other side includes environmental
factors, lifestyle factors and combination effects of some other medications.[26]
Consequently, evaluating genetic aspects such as patient response variability to
drugs, and drug toxicity is essential in achieving personal medicine. So, genetic
information can be used by clinicians in drug selection process to improve
treatment efficacy, minimize potentially hazardous drug effects, and increase the
chances for success. Future developments in this area of study are sure to extend
the knowledge of genetic variation, which in turn will lead to better quality, risk-
free and personal health care.

Introducing a New Approach to the Healthcare System Based on

Personalized Pharmacology

Individualized medicine consists of targeted medication dosages which meet the

general features of genetics and other attributes of each patient. Within this
concept, program developers are no longer constrained by the idea of treatment
for all, but treatment that has the least possible side effects and the best
improvement rate possible. Personalized pharmacology is now in the process of
achieving new standards of pinpoint accuracy and efficacy through the gains of
pharmacogenomics, bioinformatics, and molecular diagnostics.[27] Perhaps the
most obvious way in which personalized pharmacology is transforming medicine
is genetics. In this knowledge management system, clinicians are able to
determine how a patient is likely to react to certain chemicals in drugs based on
genetic pattern of the individual. It also makes it possible to choose those drugs
and their doses that would be most effective without posing the risk of creating
side effects. For example, testing for the polymorphisms in the CYP2D6&
CYP2C19 gene in patients developed for depression and antiplatelet treatments
means that the physicians can give effective results. Similarly, oncologists can
choose drugs based on tumor specific genetic markers like Her2/neu over
expression to choose trastuzumab and has better survival with lesser
toxicities.[28]

Personalized pharmacology also changes the approach to chronic diseases, which

are characterized by long and often intricate treatment with use of drugs. For
example, in cardiovascular medicine, genetic testing of SLCO1B1 variants enables
computation of patients susceptible to statin-induced myopathy to make new
treatment regimens. In diabetes treatment, pharmacogenomics aspects help to
determine the medication, such as sulfonylureas or metformin, according to
genetic profiles. These specific strategies improve compliance with therapy and
long-term health results. Apart from self-advantages, personalized pharmacology
has enormous opportunities to advance the popular health. This means that,
through determination of the factors that need to be inherited for a particular
variation to be correct in a given population, then population specific treatment
programs can be developed. This is especially important given the fact that
present day global trends indicate that certain genetic pockets within certain
ethnic groups may not respond well to present line drug combo. For instance,
 1853

there exists genetic variations especially related to warfarin metabolism in

particular ethnical groups and therefore, requires a change in dosing to have a
huge cover crops and be efficient at the same time. Other such measures help in
eradicating the problem of inequality in the treatment of patients.[29]
Furthermore, analyzing people’s genomes helps prevent adverse drug reactions
(ADRs), which are the major reason for hospitalizations and increased expenses.
Genotyping for the HLA-B alleles has helped avert severe adverse reactions to
certain medications including batcaver and carbamazepine. In case of treatment
planning, the at-risk patient population may be known before undergoing
therapies that are ineffective or even toxic, which would benefit patient safety and
also decrease the costs on healthcare.[30]

It also reaffirms the patient-centered medicine in which pharma placed an

emphasis on it through adopting pharmacology. This inevitably makes patient
more trusting, attentive and compliant with treatment decisions which would
otherwise be unfulfilled due to lack of such genetic understanding. Furthermore,
they found that the expansion of technologies, including EHRs incorporating
pharmacogenomics data for clinical analysis and cross-professional collaboration,
improve the quality of care that can be provided to patients.[31] There are,
however, a number of issues which lie ahead of the implementation of the
personalized pharmacology. The major challenges which have been identified
include; expensive costs Of performance of the genetic tests, coupled with lack of
expanded access in low economically developed areas, inadequate provider
training. In addition, distributional equity based concerns such as privacy, data
protection and genetic discrimination are major challenges that seek equitable
and responsive intervention. In the future, as people conduct research in
personalized pharmacogenomics and pharmaceutical technology develops deeper,
the aspects of personal pharmacology will extend to include gene editing or RNA
Based therapies etc. These innovations claim to be capable of treating diseases
that were until now untreatable, and further increase the accuracy of medicine.
Personalized pharmacology will change the approach to health and medicine
administration by making it safer, more effective, and unique for each patient
around the globe.[32]

Drug Metabolism Variability: John, The Roadmap to Optimal Outcomes

Pharmacokinetics, the differences in the rates of drug metabolism are the

foundation of individualized approach to treatment based on the patient’s genetic
and physiological characteristics. Pharmacokinetics which is the study of how
drugs are absorbed, distributed, metabolized and excreted by the body is affected
by genetic factors, age, sex, organ function and exposure to certain factors. These
differences are critical because they define how drugs will work, for better and for
worse, in patients’ bodies and dictates the result of treatments pegged on these
medicines.[33] Personal variation in drug metabolizing enzymes is governed
purely by genetic factors in terms of genetic polymorphisms. The CYP enzyme
family that is involved in the metabolism of most drugs has been reported to vary
so much from one individual to another. For instance, the genetic variation
determines the CYP2D6 gene so that patients can be easily characterized as PMs,
IMs, EMs, or UMs. Originally, drug efficacy and safety are embedded in these
classifications. In effect, poor metabolizers were likely to have drug build up and
1854

toxicity while ultra-rapid metabolizers were likely to exhibit poor efficacy due to
rapid elimination. This alone points in part to the need for genetic testing in order
to inform rational choice of drug and dosage. Another important enzyme subject
to genetic polymorphism is CYP2C19 which includes clopidogrel and proton pump
inhibitors in its list of metabolized medications. Those with reduced-function
CYP2C19 receive a weaker activation of the medicine, thus increasing the
likelihood of cardiovascular events. On the other hand, the effects of PPIs may be
long-standing in these patients, making necessary, changes in the dosage. Such
knowledge enables the clinician to deliver treatment that is effective as well as
safe to the recipient of the treatment.[34]

Apart from hereditary influences, eating habits, tobacco, alcohol and some other
drugs, additional medicines can influence the rate of drug metabolism. For
example, grapefruit juice can delay the working of CYP3A4 enzyme thereby
slowing up the metabolisms of statins and calcium channel blockers. Like it,
smoking promotes expression of CYP1A2 that increases the metabolism of drugs
like theophylline and some antipsychotic medications. Assurance of these
interactions is important in order to fit treatments to a specific patient’s life
schedules. Inter-individual variability in drug metabolism is also seen in regard to
specific populations. For example, the patients in children and elder groups may
suffer from different metabolic capability than adults owing to a less developed or
damaged organ system. This is the case because in neonates, the
biotransformation enzyme systems are still immature, and hence the drug half-
life is long, raising the risk of toxicity. On the other hand, hepatic and renal
function may be compromised in elderly patients with a resultant increase in
susceptibility to adverse effects through alteration of the dose rate. All of these
age related issues have to be taken into account when planning therapy to avoid
adverse effects of the treatment on the patient.[35]

Thus, sex-based difference in drug metabolism also emphasizes the importance of

personalized therapy. Sex-based differences in hormonal regulation of drug-
metabolizing enzymes are related to different rates of drug clearance. For
instance, women may take some medicine like zolpidem slowly than men because
of which it prolongs its action and increases the chances of side effects. Al of
these make it imperative to identify such differences in order to enhance gender
specific treatment. The general importance of the inter-individual variability in
drug metabolism is probably best illustrated by its relation to ADR. Metabolic
inter-individual differences may create conditions within the body in which the
drug concentration is too low to eradicate pathogens or too high to be safely
tolerated. For example, patients with low TPMT enzyme activity are likely to
develop serious bone marrow suppression when administered thiopurine drugs.
Recognizing such genetic and metabolic distinctions facilitates prevention of such
risks in the form of dose changes or various therapies. New pharmacogenomics
test has brought forth metabolism predictors of drugs before the prescription
stage, enabling precision treatment. These tests are very useful in predicting the
likely impact of a person’s genetic profile on drug metabolism then prescribe the
appropriate drugs and the right dosage that is likely going to respond well. Since
these technologies are growing more popular and cheap, their implementation
Into the clinical setting routine will also improve the capability of target
care.[36,37,38] Therefore, variability in drug metabolism is one of the necessary
 1855

approaches to reaching individual therapy goals and maximal efficacy and safety.
This insight into genetic, environmental, and physiology differences allows
providers to break free from theálu cliché mold of treatment and come up with
innovative solutions that fit the patients’ needs to a T. In doing so, this approach
benefits the quality of care as well as becomes a foundation for the future where
people rather than diseases will be treated.[39,40]

Conclusion

Therefore, it is safe to conclude that drug metabolism variation is one of the

biggest reasons for the differences in personalized pharmacotherapy. With further
knowledge in genetic variations affecting drug metabolism, it is slowly
transitioning to the norm to have people receive treatment unique to them.
Pharmacogenomics testing has the ability to enhance patient outcomes by
determining drug susceptibility in patients, to get the right drug for the right
person and right dose and also the wrong drug for the wrong patient and wrong
dose. As technology progresses and different methods in genetic testing become
available to a broader range of the population, healthcare providers are better
equipped and more capable to make decisions that in addition to improving the
outcomes of the cure, also prevents contra indications such as more negative
reactions from occurring to the body when taking certain drugs. The inclusion of
drug metabolism variability into clinical practice is a new revolution in the
medical field that will pave way to better safety, effectiveness and patient tailored
in the global society.

References

1. Adebukola, A. A., Navya, A. N., Jordan, F. J., Jenifer, N. J., & Begley, R. D.
(2022). Cyber security as a threat to health care. Journal of Technology and
Systems, 4(1), 32-64.
2. Bank, P. C., Swen, J. J., & Guchelaar, H.-J. (2018). Implementation of
pharmacogenomics in everyday clinical settings. Advances in Pharmacology,
83, 219-246.
3. Brown, L., Eum, S., Haga, S. B., Strawn, J. R., & Zierhut, H. (2020). Clinical
utilization of pharmacogenetics in psychiatry—perspectives of pharmacists,
genetic counselors, implementation science, clinicians, and industry.
Pharmacopsychiatry, 53(04), 162-173.
4. Cacabelos, R., Cacabelos, N., & Carril, J. C. (2019). The role of
pharmacogenomics in adverse drug reactions. Expert Review of Clinical
Pharmacology, 12(5), 407-442.
5. Carr, D. F., Turner, R. M., & Pirmohamed, M. (2021). Pharmacogenomics of
anticancer drugs: Personalizing the choice and dose to manage drug
response. British Journal of Clinical Pharmacology, 87(2), 237-255.
6. Cheng, J. W. (2018). Current perspectives on the role of the pharmacist in
heart failure management. Integrated Pharmacy Research and Practice, 1-11.
7. Daly, A. K. (2017). Pharmacogenetics: A general review on progress to date.
British Medical Bulletin, 124(1), 65-79.
8. Ellithi, M., Baye, J., & Wilke, R. A. (2020). CYP2C19 genotype-guided
antiplatelet therapy: Promises and pitfalls. Pharmacogenomics, 21(12), 889-
897.
1856

9. Gammal, R. S., & Fieg, E. (2022). Pharmacist and genetic counselor

collaboration in pharmacogenomic testing. Journal of Genetic Counseling,
31(4), 1298-1312.
10. Gammal, R. S., Lee, Y. M., Petry, N. J., Iwuchukwu, O., Hoffman, J. M.,
Kisor, D. F., & Empey, P. E. (2022). Pharmacists leading the way to precision
medicine: Updates to the core pharmacist competencies in genomics.
American Journal of Pharmaceutical Education, 86(4), 1-9.
11. Hayashi, M., Hamdy, D. A., & Mahmoud, S. H. (2022). Applications for
pharmacogenomics in pharmacy practice: A scoping review. Research in
Social and Administrative Pharmacy, 18(7), 3094-3118.
12. Hicks, J. K., Aquilante, C. L., Dunnenberger, H. M., Gammal, R. S., Funk, R.
S., Aitken, S. L.,... Elder, C. T. (2019). Precision pharmacotherapy:
Integrating pharmacogenomics into clinical pharmacy practice. Journal of the
American College of Clinical Pharmacy, 2(3), 303-313.
13. Hicks, J. K., Howard, R., Reisman, P., Adashek, J. J., Fields, K. K., Gray, J.
E.,... Perkins, R. M. (2021). Integrating somatic and germline next-generation
sequencing into routine clinical oncology practice. JCO Precision Oncology, 5,
884-895.
14. Ji, Y. (2018). Applications of pharmacogenomics in oncology. Advances in
Molecular Pathology, 1(1), 115-124.
15. Joly, Y., & Avard, D. (2020). Pharmacogenomics: Ethical, social, and public
policy issues. In The Road from Nanomedicine to Precision Medicine (pp. 791-
827). Jenny Stanford.
16. Lee, C. R., Sriramoju, V. B., Cervantes, A., Howell, L. A., Varunok, N., Madan,
S.,… Clarke, M.(2018). Clinical outcomes and sustainability of using
CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary
intervention. *Circulation: Genomic and Precision Medicine, 11(4), e002069.
17. Luke, M. J., Krupetsky, N., Liu, H., Korenvain, C., Crown, N., Toenjes, S.,
McCarthy, L. M. (2021). Pharmacists as personalized medicine experts
(PRIME): Experiences implementing pharmacist-led pharmacogenomic testing
in primary care practices. Pharmacy, 9(4), 201.
18. Maduka, C. P., Adegoke, A. A., Okongwu, C. C., Enahoro, A., Osunlaja, O., &
Ajogwu, A. E. (2023). Review of laboratory diagnostics evolution in Nigeria's
response to COVID-19. International Medical Science Research Journal, 3(1),
1-23.
19. Master, Z., Smith, C., & Tilburt, J. C. (2020). Informed consent for stem cell-
based interventions. JAMA, 323(9), 893-893.
20. Miao, L., Zhang, J., Yi, L., & Huang, S.(2020). The ethical, legal, and
regulatory issues associated with pharmacogenomics. Pharmacogenomics in
Precision Medicine: From a Perspective of Ethnic Differences, 219-239.
21. Okunade, B. A., Adediran, F. E., Maduka, C. P., & Adegoke, A. A. (2023).
Community-based mental health interventions in Africa: A review and its
implications for US healthcare practices. International Medical Science
Research Journal, 3(3), 68-91.
22. Orrico, K. B. (2019). Basic concepts in genetics and pharmacogenomics for
pharmacists. Drug Target Insights, 13, 1177392819886875.
23. Remsberg, C. M., Bray, B. S., Wright, S. K., Ashmore, J., Kabasenche, W.,
Wang, S.,… Daoud, S. S. (2017). Design, implementation, and assessment
approaches within a pharmacogenomics course. American Journal of
Pharmaceutical Education, 81(1), 11.
 1857

24. Rayhan, R., & Rayhan, S. (2023). AI and human rights: Balancing innovation
and privacy in the digital age. In DOL.
25. Satam, H., Joshi, K., Mangrolia, U., Waghoo, S., Zaidi, G., Rawool, S.,… Das,
G. (2023). Next-generation sequencing technology: Current trends and
advancements. Biology, 12(7), 997.
26. Shendure, J., Findlay, G. M., & Snyder, M. W. (2019). Genomic medicine-
progress, pitfalls, and promise. Cell, 177(1), 45-57.
27. Singh, P. (2023). Pharmacogenomics advances: Customizing drug therapies
for individual patients. Journal of Advanced Research in Pharmaceutical
Sciences and Pharmacology Interventions, 6(1), 21-27.
28. Ta, R., Cayabyab, M. A., & Coloso, R. (2019). Precision medicine: A call for
increased pharmacogenomic education. Personalized Medicine, 16(3), 233-
245.
29. Veilleux, S., & Bouffard, M. (2019). Knowledge and understanding of
pharmacogenomic testing among patients and health care professionals: A
scoping review. Patient Education and Counseling, 102(11), 2001-2009.
30. Veilleux, S., Bouffard, M., & Bourque Bouliane, M. (2020). Patient and health
care provider needs and preferences in understanding pharmacogenomic and
genomic testing: A meta-data analysis. Qualitative Health Research, 30(1),
43-59.
31. Ayo-Farai, O., Olaide, B.A., Maduka, C.P., & Okongwu, C.C. (2023).
Engineering innovations in healthcare: A review of developments in the USA.
Engineering Science & Technology Journal, 4(6), 381-400.
32. Babarinde, A.O., Ayo-Farai, O., Maduka, C.P., Okongwu, C.C., Ogundairo,
O., & Sodamade, O. (2023). Review of AI applications in healthcare:
Comparative insights from the USA and Africa. *International Medical
Science Research Journal, 3*(3), 92-107.
33. Barker, C. I., Groeneweg, G., Maitland-van der Zee, A. H., Rieder, M. J.,
Hawcutt, D. B., Hubbard, T. J., & Carleton, B. C. (2022). Pharmacogenomic
testing in paediatrics: Clinical implementation strategies. British Journal of
Clinical Pharmacology, 88*(10), 4297-4310.
34. Bishop, I. R., Schneiderhan, M. E., Butler, T., Carpentier, R. M., Heins, K. R.,
& Formea, C. M. (2023). Pharmacogenomics to support mental health
medication therapy management: Clinical practice considerations and a
conceptual framework to enhance patient care. Journal of the American
College of Clinical Pharmacy.
35. Fahim, S. M., Alexander, C. S. W., Qian, J., Ngorsuraches, S., Hohmann, N.
S., Lloyd, K. B., … & Westrick, S. C. (2023). Current published evidence on
barriers and proposed strategies for genetic testing implementation in
healthcare settings: A scoping review. Journal of the American Pharmacists
Association.
36. Fragala, M. S., Shaman, J. A., Lorenz, R. A., & Goldberg, S. E. (2022). Role of
pharmacogenomics in comprehensive medication management:
Considerations for employers. *Population Health Management, 25(6), 753-
762.
37. Gambardella, V., Tarazona, N., Cejalvo, J. M., Lombardi, P., Huerta, M.,
Roselló, S., & Cervantes, A. (2020). Personalized medicine: Recent progress in
cancer therapy. Cancers, 12(4), 1009.
38. Hassan, M., Awan, F. M., Naz, A., deAndrés-Galiana, E. J., Alvarez, O.,
Cernea, A., & Kloczkowski, A. (2022). Innovations in genomics and big data
1858

analytics for personalized medicine and healthcare: A review. *International

Journal of Molecular Sciences, 23(9), 4645.
39. Jarvis, J. P., Peter, A. P., Keogh, M., Baldasare, V., Beanland, G. M.,
Wilkerson, Z. T., & Shaman, J. A. (2022). Real-world impact of a
pharmacogenomics-enriched comprehensive medication management
program. Journal of Personalized Medicine, 12(3), 421.
40. Kabbani, D., Akika, R., Wahid, A., Daly, A. K., Cascorbi, I., & Zgheib, N. K.
(2023). Pharmacogenomics in practice: A review and implementation guide.
Frontiers in Pharmacology, 14, 1189976.
 ‫‪1859‬‬

‫دور علم الوراثة الدوائية في الطب الشخصي‪ :‬تركيز على تمثيل األدوية في الجسم‬
‫الملخص‬
‫الخلفية‪ :‬النهج التقليدي في عالج األدوية غالبًا ما يعتمد على عالجات موحدة دون مراعاة التباين الفردي في أيض األدوية‪ .‬ومع‬
‫نهجا أكثر‬
‫التقدم في علم الصيدلة الجينية‪ ،‬تم تسليط الضوء على أهمية العوامل الوراثية والبيئية في عملية األيض‪ ،‬مما يوفر ً‬
‫صا في الطب‪.‬‬ ‫تخصي ً‬
‫الهدف‪ :‬يهدف البحث إلى استكشاف دور تباين األيض في الطب المخصص وكيفية تحسين النتائج العالجية وتقليل التفاعالت‬
‫الدوائية السلبية من خالل تخصيص العالجات بنا ًء على العوامل الوراثية والبيئية‪.‬‬
‫الطرق‪ :‬تم إجراء مراجعة شاملة لألدبيات لفحص تأثير العوامل الوراثية والبيئية على عملية األيض‪ .‬كما تم استكشاف دور‬
‫اختبارات الصيدلة الجينية في تخصيص العالجات‪.‬‬
‫يؤثر بشكل كبير على األيض والفعالية العالجية والسالمة‪ .‬كما أن ‪CYP‬النتائج‪ :‬أظهرت النتائج أن التباين الوراثي في إنزيمات‬
‫دورا مه ًما في النتائج العالجية‪.‬‬
‫العوامل البيئية مثل النظام الغذائي وأسلوب الحياة تلعب ً‬
‫الخالصة‪ :‬يعد تباين األيض من العوامل األساسية في تطوير العالجات المخصصة‪ .‬من خالل دمج اختبارات الصيدلة الجينية في‬
‫الممارسة السريرية‪ ،‬يمكن تحسين نتائج العالج وتقليل المخاطر‪ ،‬مما يساهم في تحسين سالمة المرضى وفعالية العالج‪.‬‬
‫الكلمات المفتاحية‪ :‬أيض األدوية‪ ،‬الصيدلة الجينية‪ ،‬الطب المخصص‪ ،‬التباين الوراثي‪ ،‬التفاعالت الدوائية السلبية‪ ،‬اختبار الصيدلة‬
‫الجينية‪.‬‬