Considering malaria is a highly devastating disease of mankind, total eradication of malaria seems to be an uphill task, the only relief from this disease is achieved by usage of antimalarial drugs. Since malaria is associated with humans from time immemorial, usage of traditional substances to most presently effective antimalarial have been recorded to cure this disease. With the advent of modern biological techniques aided the understanding of the biochemical pathways of antimalarial metabolism thereby helping in designing successful usage of many antimalarials. Nevertheless, improper usages of certain drugs have led to the origin and spread of drug resistant malaria parasites (chloroquine resistant Plasmodium falciparum). Also, the genetic basis of antimalarial metabolism in humans is now well understood and frequent mutations in genes of malarial parasites are well associated with drug resistance. The entire scenario of antimalarial usage in the field have become complicated, partly due to poor understanding between antimalarial metabolism in humans and drug fighting mechanism in parasites, by which resistance to even combined therapy (e.g. Artemisinin Combination Therapy) have started emerging. Vital basic understanding from human and parasite population genetics (involving antimalarial both metabolizing genes in human and resistant genes in parasite) could be an ideal starting point to malaria control.

1. Antimalarial metabolization: what have we learnt so far?
WJPP
Antimalarial metabolization: what have we learnt so
far?
Naazneen Khan1*
and Abdullah Chand2
1*
Evolutionary Genomics and Bioinformatics Laboratory, Division of Genomics and Bioinformatics, National Institute of
Malaria Research, Sector-8, Dwarka, New Delhi-110077, India.
2
CMJ University, Shillong, Meghalaya, 793 003, India.
Considering malaria is a highly devastating disease of mankind, total eradication of malaria
seems to be an uphill task, the only relief from this disease is achieved by usage of antimalarial
drugs. Since malaria is associated with humans from time immemorial, usage of traditional
substances to most presently effective antimalarial have been recorded to cure this disease.
With the advent of modern biological techniques aided the understanding of the biochemical
pathways of antimalarial metabolism thereby helping in designing successful usage of many
antimalarials. Nevertheless, improper usages of certain drugs have led to the origin and spread
of drug resistant malaria parasites (chloroquine resistant Plasmodium falciparum). Also, the
genetic basis of antimalarial metabolism in humans is now well understood and frequent
mutations in genes of malarial parasites are well associated with drug resistance. The entire
scenario of antimalarial usage in the field have become complicated, partly due to poor
understanding between antimalarial metabolism in humans and drug fighting mechanism in
parasites, by which resistance to even combined therapy (e.g. Artemisinin Combination
Therapy) have started emerging. Vital basic understanding from human and parasite population
genetics (involving antimalarial both metabolizing genes in human and resistant genes in
parasite) could be an ideal starting point to malaria control.
Key words: Malaria, antimalarial drugs, metabolization, population genetics, pharmacogenomics
INTRODUCTION
Malaria is considered as one of the three most deadly
infectious diseases including Tuberculosis (T.B.) and
Human Immunodeficiency Virus (HIV) (Riley and Stewart,
2013) which has resulted in high mortality worldwide with
an estimated 3.3 million people at high risk malaria
(World Health Organization, 2013). It affects, mainly,
population residing in tropical and subtropical areas due
to the presence of suitable temperature and rainfall which
is required for the development of Plasmodium parasites
in female Anopheles mosquitoes (Gallup and Sachs,
2001). Over 90% of malaria sufferers are borne by
populations in Africa (Winstanley et al., 2004) and are
mainly children (<5 years) and pregnant women. Outside
Africa, malaria affects densely populated countries such
as Indian subcontinent and Southeast Asia where the
prevalence of P. falciparum, P. vivax and recently
increased P. knowlesi are endemic.
Corresponding Author: Dr. Naazneen Khan, National
Institute of Malaria Research, Sector-8, Dwarka, New
Delhi-110077, India. E-mail addresses:
naaz.27khan@gmail.com
World Journal of Pharmacy and Pharmacology
Vol. 1(1), pp. 002-010, July, 2015. © www.premierpublishers.org, ISSN: 1926-8398x
Review

2. Antimalarial metabolization: what have we learnt so far?
Khan and Chand 002
Malaria is a devastating disease caused by different
Plasmodium species, Plasmodium falciparum,
Plasmodium vivax, Plasmodium ovale and Plasmodium
malariae. Among the four species, Plasmodium
falciparum is the most virulent and is a major cause of
high morbidity and mortality in endemic regions (Boland,
2001). These parasites have complex life cycles in both
human host and vector (Hyde et al., 2007) that starts with
the inoculation of sporozoites into the human dermis
which further infects the liver within 1-2 hr and invade
hepatocytes, releasing merozoites in the blood stream.
These merozoites undergo rapid multiplication and forms
sexual stages that await ingestion by mosquitoes for
further development of zygote that develops into oocyst
forming thousands of sporozoites. Further, these
sporozoites migrate to the salivary glands of mosquitoes
and can be injected into new host upon next blood meal
(Hyde et al., 2007). In order to hinder the pathogenesis
and further transmission of malaria, each developmental
stage of the parasite represents potential target for the
development of antimalarial.
The most significant period in the history of malaria
control was started when a conference was organized by
World Health Organization, held in Kampala, Uganda in
1950 (Winstanley et al., 2004) which was named “Global
Malaria Eradication Programme”. Initially, the campaign
was started with the use of pesticide DDT and
chloroquine, which was found to be successful in regions
of low malaria transmission such as Sri Lanka, China,
Latin America, Southern Europe, southern part of the
United States, Southern region of Soviet Union (Sachs,
2002). Despite these successes, there was re-
emergence of chloroquine-resistant Plasmodium
parasites and DDT-resistant Anopheles mosquitoes in
areas where it had been eliminated (Sachs, 2002). As a
consequence, the concept of malaria eradication was
dropped in favour of malaria control and the focus was
totally shifted on the development of cost effective drug
strategies. This programme was successful in countries
with developed economy like Thailand having better
health infrastructure (Chareonviriyaphap et al., 2000), but
it failed in poor tropical countries that resulted in the
withdrawal of Global eradication programme in 1972.
Furthermore, the dramatic increase in cases of malaria
led to the adoption of Roll Back Malaria (RBM) that was
launched by a consortium of World Health Organization,
World Bank, United Nation Development Programme and
United Nation Children‟s Fund (UNICEF) in 1998 (Brito,
2001).
Despite enormous efforts taken to eradicate and control
malaria, it is still uncontrollable mainly because of
poverty, low economic status and environmental
conditions (temperature and rainfall) that lead to
emergence of drug resistant parasites. In this review
article, progress in the study of different drug
metabolizing gene involved in antimalarial metabolism is
presented with special emphasis on their mode of action
and genetic overview.
History of Antimalarial usage
The effort for the eradication of malaria was started long
ago before the use of Chloroquine. Several remedies
were tried to treat malaria since time-immemorial which
were totally based on the superstitious thought such as,
opium laced beer, skull operations etc. In the nineteenth
century, the first antimalarial “Quinine” was extracted
from Cinchona bark and was used for more than 350
years to effectively treat malaria. It remained the
mainstay of antimalarials till 1920‟s, when more synthetic
antimalarials became available. Although, Quinine was
effective against malaria, the extraction cost was quite
high and it also causes side effects (Brito, 2001). During
this period, Chloroquine was introduced due to its
effectiveness against all forms of malaria and cheap
manufacturing cost. With the heavy usage of chloroquine,
the cases of resistant Plasmodium falciparum emerged
and become widespread in almost all areas of the world
(Wellems and Plowe, 2001). Moreover, in the twentieth
century, the discovery of Chinese herb “Qinghao” was
marked as one of the greatest discoveries in the scientific
world as its extracts form the basic ingredient for
artemisinin and its derivatives that were found to be more
effective than quinine. While quinine is effective against
mature parasite stages, artemisinin acts against all
asexual and sexual stages of parasites. Before
artemisinin could be declared as an ideal antimalarial
candidate, there was an emergence of artemisinin
resistant parasites outbreaks in regions of Southeast Asia
(Phyo et al., 2012). The emergence of resistivity to known
drugs ignited the idea of combination therapies. World
Health Organization has also recommended drug
combinations to delay the emergence and spread of drug
resistance. The first combination drug was “Fansidar”
formed by amalgamating Sulphadoxine and
Pyremethamine antimalarial compounds (Alessandro and
Buttiens, 2001). In recent years, WHO declared
artemisinin combination therapies (ACT) as a first line
treatment for uncomplicated Plasmodium falciparum (Li
and Zhou, 2010).
Antimalarial drug metabolizing pathways
Since malaria is associated with humans from time
immemorial, usage of various traditional substances to
most presently effective drugs as antimalarial have been
documented. These drugs help in curing the disease but
at the same time persist in the body where they
accumulate to toxic level which led to adverse drug
reactions, therapeutic drug failure and susceptibility to
other diseases. These drugs need to be metabolized and
detoxified from the body as quickly as possible. Thus, the

3. Antimalarial metabolization: what have we learnt so far?
World J. Pharm. Pharmacol. 003
Figure 1. Antimalarials metabolized by drug metabolizing gene (a. Primaquine, b. Artemisinin, c. Proguanil, d. Dapsone, e. Amodiaquine, f.
Chloroquine, g. Clindamycin, h. Mefloquine, i. Halofantrine and j. Sulphadoxine).
effective metabolization and detoxification of drugs is key
to therapeutic drug efficacy and this is carried out via two
main reactions; Phase I and Phase II catalyzed by drug
metabolizing enzyme. While Phase I reaction is primarily
catalyzed by Cytochrome P450 enzymes (CYP), Phase II
reactions are catalyzed by many enzymes viz.
Acetyltransferase, Gucuronosyltransferase, Glutathione-
s-transferase and Sulphotransferases (Goldstein and
Faleto, 1993). Furthermore, based on the effective
metabolization by drug metabolizing enzyme, some drugs
are metabolized by single enzyme (metoprolol by
CYP2D6), whereas, others involve two or more enzyme
for their metabolization (warfarin by CYP1A2, CYP2D6
and CYP3A4) (Lynch and Price, 2007). Hence, it was
observed that the effective action of drug to its target
mainly depends on its effective metabolization and
detoxification. In this review article, we have discussed
about the ten different antimalarial metabolized by one or
more drug metabolizing enzyme and their mode of action:
Primaquine: The antimalarial Primaquine is one of the
important drugs that is effective against the exo-
erythrocytic stages of Plasmodium vivax and Plasmodium
ovale and gametocytic stages of Plasmodium falciparum
(Edwards et al., 1993).
Mode of action: Primaquine disrupts the metabolic
processes of Plasmodium mitochondria by interfering
with the function of ubiquinone as an electron carrier in
the respiratory chain (Hill et al., 2006).
Drug metabolizing enzyme: Primaquine is primarily
converted to metabolite carboxyprimaquine by CYP1A2
(Figure 1a). (Hill et al., 2006), and is also metabolized by
CYP3A4 (Kerb et al., 2009).
Artemisinin: Artemisinin is an antimalarial extracted from
Qinghao (blue-green herb) (Hsu, 2006) and is used in
severe malaria and is effective against all the blood
stages of Plasmodium falciparum including the youngest
(ring form) stage of the parasite (WHO, 2006).
Mode of action: - The endoperoxide bridge of Artemisinin
interacts with haem to produce free radicals that alkylate
protein and damage the micro-organelles and membrane
of the parasite. It also interrupts with the haemoglobin
catabolism system causing inhibition of haemoglobin
degradation and polymerization of haem to haemozoin
which is used by parasite as its nutritional requirements
(Pandey et al., 1999).
Drug metabolizing enzyme: Artemisinin is mainly
metabolized to dihydroartemisinin by CYP2B6 (Malhotra
et al., 2006; Figure 1b). However, the other metabolizing
enzymes also involved in the metabolism of artemisinin
are CYP3A4 and CYP2A6 (Svesson and Ashton, 1999).
Proguanil: Proguanil is an antimalarial drug used for the
treatment of malaria caused by Plasmodium falciparum
(Pang et al., 1989).
Mode of action: - Proguanil inhibits dihydrofolate
reductase (DHFR) enzyme essential for synthesis of
parasite DNA (Boggild et al., 2007).

4. Antimalarial metabolization: what have we learnt so far?
Khan and Chand 004
Drug metabolizing enzyme: - Proguanil is converted to its
active metabolite Cycloguanil by CYP2C19 (Figure 1c).
Additionally, CYP3A4 have a limited role in the
metabolism of Proguanil to Cycloguanil (Brentano et al.,
1997).
Dapsone: - Dapsone is a 4, 4‟-diamnodiphenyl sulphone
and widely used for the treatment of Leprosy,
Chloroquine resistant malaria and Dermatitis
Herpetitiformis. It is effective against the treatment of
schizonticidal and gametocidal activity of Plasmodium
falciparum, but does not act against asexual form of the
Plasdmodium vivax. (Saha et al., 2003).
Mode of action: - Dapsone inhibits folic acid synthesis of
parasite by inhibiting DHFR enzyme (Tingle et al., 1997).
Drug metabolizing enzyme:-Dapsone is metabolized by
CYP2C9 (Tingle et al., 1997), CYP3A4 (Adedayo et al.,
1998) and NAT2 (Louet et al., 1999) (Figure 1d).
Amodiaquine: Amodiaquine is derived from quinoline
and is more effective as compared to chloroquine against
Plasmodium falciparum (Li et al., 2002).
Mode of action: The mode of action against the parasite
is same as that of chloroquine, by inhibiting
polymerization of haem and thus, inhibiting formation of
toxic haemozoin. (Hombhanje et al., 2004).
Drug metabolizing enzyme: - Amodiaquine is converted to
N-Desethylamodiaquine by CYP2C8 (Li et al., 2002;
Figure 1e).
Chloroquine: The quinoline containing antimalarials are
effective against malaria parasite Plasmodium falciparum
(Krogstad et al., 1998).
Mode of action: Chloroquine is a dibasic drug, which
diffuses down the pH gradient and accumulates in the
acidic vacuole of the parasite Plasmodium. The high
intravacuolar concentration of chloroquine inhibits the
polymerization of the haem. As a result the haem which is
released during haemoglobin breakdown builds up to
poisonous levels, killing the parasite (Foley and Tilley,
1997).
Drug metabolizing enzyme: Chloroquine is metabolized
by CYP3A4 to N-desethylchloroquine (Cooper and
Magware, 2008, Figure 1f).
Clindamycin: Clindamycin is semisynthetic derivative of
Lincomycin and is effective against many species
including Plasmodium sp.(Lell and Kremsner, 2002).
Mode of action: Clindamycin slowly accumulates inside
the apicoplast of Plasmodium sp. and killing it ultimately
(Lell and Kremsner, 2002).
Drug metabolizing enzyme: Clindamycin is metabolized
by CYP3A4 to Clindamycin sulfoxide (Wynalda et al.,
2003, Figure 1g).
Halofantrine: A phenanthrene methanol derivative used
as antimalarial drugs against uncomplicated chloroquine
and multidrug resistant Plasmodium falciparum (Halliday
et al., 1995).
Mode of action: - Halofantrine is blood schizonticides and
affects only trophozoites and schizonts in the red blood
cells. It binds to ferriprotoporphyrin IX in red blood cells
affected by Plasmodium and form toxic complexes that
damage the parasite membrane (Nothdruft, 1993).
Drug metabolizing enzyme: - Halofantrine is metabolized
by CYP3A4 to N-debutylhalofantrine (Baune, 1999;
Figure 1h).
Mefloquine: -Mefloquine antimalarial is effective against
the chloroquine resistant strains of Plasmodium
falciparum (Riviere et al., 1985).
Mode of action:-The quinoline binds to high density
lipoproteins (HDL) in the serum and delivered to the
erythrocytes, where they interact with an erythrocyte
membrane protein stomatin and are then transferred to
the intracellular malaria parasite.
Drug metabolizing enzyme: - Mefloquine is metabolized
by CYP3A4 (Khaliq et al., 2001, Figure 1i).
Sulphadoxine: - Sulphadoxine is a sulphonamide and is
effective against Plasmodium falciparum. It is used in
combination with other drugs to treat malaria ((Seaton et
al., 2000).
Mode of action: - Sulphadoxine inhibits folic acid
biosynthesis by blocking the formation of dihydrofolic acid
and inhibiting dihydropteroate synthase (DHPS) enzyme
(Ridley et al., 2002).
Drug metabolizing enzyme: -Sulphadoxine is metabolized
by NAT2 (Fuchs, 2004; Melmon, 2000; Figure 1j).
Genetic overview of antimalarial metabolizing genes
Since the advent of new agricultural techniques, changes
in environmental condition, subsistence strategies and
dietary habits had sculpted the human genome that led to
the emergence of different complex diseases. In order to
cure or treat a disease, patients are administered drugs
that are chemical in nature, hence their metabolization
and detoxification in the body is essential. For effective
metabolization, human body is armed with drug
metabolizing enzyme for effective metabolization and
detoxification of exogenous and endogenous
compounds. We herewith, represented the detailed
information about the drug metabolizing gene located on
human chromosome with number of exons and introns
involved in metabolism of anti-malarials.
CYP1A subfamily: - In humans, there are two members
of CYP1A family: CYP1A1 and CYP1A2 that play a major
role in the biotransformation of food and environmental
pollutants. The human CYP1A2 is involved in the
metabolism of antimalarial primaquine and spans a gene
length of 7758 bp (Chromosome 15q24.1, position

5. Antimalarial metabolization: what have we learnt so far?
World J. Pharm. Pharmacol. 005
Figure 2. Gene location, Exon, Intron of drug metabolizing gene CYP1A2 located on human chromosome 15.
Figure 3. Gene location, Exon, Intron of drug metabolizing gene CYP2B6 located on human chromosome 19.
75041184 – 75048941) with 7 exons that codes for
protein of 516 amino acid (www.ncbi.nlm.nih.gov) and
mainly expressed in the liver (Daly, 2003) (Figure 2).
CYP2B subfamily: The human CYP2B has only one
member CYP2B6 that play a significant role in the
metabolism of artemisinin. This gene spans a gene length
of 27058 bp (Chromosome 19q13.2, position 41497204-
41524301) with 9 exon (www.ncbi.nlm.nih.gov) that
codes for protein of 491 amino acid
(www.ncbi.nlm.nih.gov, Figure 3) which is highly
expressed in liver, but also expressed in the brain, small
intestine, kidney and lung (Nagata, 2002).
CYP2C subfamily: The human CYP2C has four members
viz., CYP2C18, CYP2C19, CYP2C9, and CYP2C8
clustered at human chromosome 10q24. These four
subfamily shares less than 82% amino acid identity and
significantly contribute in different ways to metabolize
drugs. Out of these four; CYP2C19, CYP2C9 and

6. Antimalarial metabolization: what have we learnt so far?
Khan and Chand 006
Figure 4. Gene location, Exon, Intron of drug metabolizing gene (A) CYP2C8, (B) CYP2C9 and (C) CYP2C19 located on human chromosome 10.
CYP2C8 were found to be most divergent. The maximum
homology is shared between CYP2C19 and CYP2C9
(90% homology), whereas, CYP2C8 share only 75%
homology identity (Kudzi et al., 2009).
CYP2C8 is more divergent among all CYP2C family
members as revealed from protein sequences. This gene
involves in the metabolism of amodiaquine and is mainly
expressed in human liver with expression level of less
than 1 (Nagata and Yamazoe, 2002). The human
CYP2C8 gene spans a gene length of 30 000 bp with 9
exons that code for 490 amino acid protein
(www.ncbi.nlm.nih.gov, Figure 4A).
CYP2C9 is also one of the major CYP2C that comprised
of one third of total hepatic P450 content. This gene plays
a pivotal role in dapsone and spans a gene length of
50734 bp (Chromosome 10q24, Position 96698415-
96749148) and contains 9 exons that codes for protein of
490 amino acid and mainly expressed in liver
(www.ncbi.nlm.nih.gov, Figure 4B).
CYP2C19 is the largest gene among human CYP450
involved in drug metabolism. The CYP2C19 gene plays a
significant role in the metabolism of proguanil and spans
a gene length of 90209 bp (Chromosome 10q24.1-q24.3,
position 96522463-96612671) and contains 9 exons that
codes for protein of 490 amino acid
(www.ncbi.nlm.nih.gov, Figure 4C), which is mainly
expressed in the liver (Nagata and Yamazoe, 2002).
Cytochrome P450 3A (CYP3A):- The human CYP3A
family composed of 25% - 30% of total hepatic
cytochromes P450 (Shimada, 1994). The CYP3A gene
family is the most important drug metabolizing gene
which is involved in the metabolization of almost 60% of
drugs. The CYP3A family comprised of 4 functional
genes: CYP3A4, CYP3A5, CYP3A7 and CYP3A43
located within 218 Kb region of chromosome 7q22.1
(www.ncbi.nlm.nih). In addition to these four functional
genes, two psuedogenes CYP3A5P1 and CYP3A5P2 are
also present (Agarwal et al., 2008). CYP3A4 exhibit
approximately 85% amino acid sequence similarity with
CYP3A5 and CYP3A7 and approximately 75% amino
acid sequence similarity with CYP3A43 (Domanski et al.,
2000).
Cytochrome P450 3A4 (CYP3A4):- CYP3A4 gene is
involved in metabolism of wide variety of antimalarial. It is
located at chromosome 7q21.3-q22.1 and spans a gene
length of 27592 bp with 13 exons (www.ncbi.nlm.nih,
Figure 5) that codes for protein of 502 amino acids which
is mainly expressed in the liver and intestine. In adults
CYP3A4 is the dominant CYP3A enzyme that plays a
dominant role in the metabolism of numerous drugs
(Hirota et al., 2004).
N-acetyltransferase (NAT):- The human N-
acetyltransferase is a broad spectrum drug metabolizing
enzyme that catalyzes N-acetylation and O-acetylation of

7. Antimalarial metabolization: what have we learnt so far?
World J. Pharm. Pharmacol. 007
Figure 5. Gene location, Exon, Intron of drug metabolizing gene CYP3A4 located on human chromosome 7.
Figure 6. Gene location, Exon, Intron of drug metabolizing gene NAT2 located on human chromosome 7.
arylamine carcinogens and heterocyclic amines present
in the exogenous chemicals including therapeutic drugs,
food and environmental pollutants. These enzymes are
located in the cytosolic liver, gut and many other tissues
of mammalian species (Dupret and Lima, 2005).
In humans, there are two functional N-acetyltransferase
(NAT) genes, NAT1 and NAT2 and one psuedogene
NATP. These functional NAT genes are located at
chromosome 8 and share 87% nucleotide and 81%
amino acid sequence identity (Windmill et al., 2000).
N-Acetyltransferase 2 (NAT2):- Human NAT2 gene
spans a gene length of 9.9 kb (Chromosome 8, positions
18,248,755 – 18,258,723) (NCBI Build 37.1 assembly,
Figure 6) and consists of a two exons, separated by a 9
kb intron. Only the second exon consists of single open
reading frame (ORF) of 873 bp that codes for 290 amino
acid and mainly expressed in liver (Fusseli et al., 2007).
The prospect of antimalarial usage lies in
pharmacogenomics
With the availability of human genome sequence, inter-
individual variation with respect to drug response has
become clear (Brockmoller and Tzevtkov, 2008) and
helped in understanding the fact that not all individual can

8. Antimalarial metabolization: what have we learnt so far?
Khan and Chand 008
equally respond to a particular drug which supports the
genetic basis of drug metabolism. In order to know the
genetic basis of gene involved in drug metabolism, the
inter-individual variation is very important. This difference
in response to drugs might be a consequence of variation
involved in drug metabolism, drug transporter or drug
receptor gene. Furthermore, these variations have
considerable effects on phenotypes, either as extensive
metabolizer (metabolism of drug is very fast and results
in low or no drug effects) or as poor metabolizer
(metabolism of drug is very slow and results in
accumulation of drug inside the body). However, it is
difficult to find, whether the whole gene family or only one
gene is involved in the inter-individual variation. Recently,
“Pharmacogenomics” emerged as a new field to study
variation in genome related to drug response. This field
helped not only in understanding the mechanism of drug
metabolism but also helped in understanding the
interaction of drugs with component of parasite (i.e
Plasmodium) and host. Additionally, Pharmacogenomics
holds the promise of personalized drug treatment, based
on underlying genetic variability of an individual (Wang
and Weinshilboum, 2008). Thus, it is very interesting to
understand that the success of any drug treatment
depends on the individual pharmacogenomic vulnerability
as well as the sensitivity of pathogen to drug. By
improving our deeper understanding and awareness of
genetic variability in drug metabolizing gene, parasite
biology and vector behavior, it is possible to reduce the
emergence and spread of drug resistance as well as
being helpful for the development of safe, cheap and
efficient drug.
CONCLUSION AND RECOMMENDATIONS
Malaria remains a major worldwide public health threat as
a result of increased drug resistance. The effective action
of drug depends on two main aspects of drug metabolism
i.e. pharmacokinetics and pharmacodynamics. Individual
susceptibility for drug response are modulated by genetic
polymorphism in the drug metabolizing gene which can
lead to drug failure, emergence of resistance, increased
toxicities, decreased safety and adverse drug reactions.
Interestingly, majority of antimalarial are metabolized by
CYP3A4 drug metabolizing gene. Despite enormous
number of studies focusing on pharmacokinetic
interaction of antimalarials with drug metabolizing gene
(Daniyan et al., 2008; Khaliq et al., 2001), little
information is known regarding relationship between
antimalarial and drug metabolizing enzyme
polymorphism. Moreover, study related to genetic
polymorphisms, drug toxicity and environmental exposure
found to be a promising area of research in controlling
the pathogenesis and eradication of the disease.
ACKNOWLEDGEMENT
The authors wish to thanks the Indian Council of Medical
Research (ICMR) for Junior and Senior Research
Fellowships.
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Accepted 24 April 2015.
Citation: Khan N, Chand A (2015). Antimalarial
metabolization: what have we learnt so far?. World
Journal of Pharmacy and Pharmacology, 1(1): 002-010.
Copyright: © 2015 Khan and Chand. This is an open-
access article distributed under the terms of the Creative
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