Drug/Small Molecule:
proguanil

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.



Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
Spartan RX CYP2C19 System CYP2C19*17, CYP2C19*2, CYP2C19*3 , rs12248560 , rs4986893 , rs4244285

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
VIP No VIP available No VIP available CYP2C19 *2A N/A N/A N/A
VIP No VIP available No VIP available CYP2C19 *3A N/A N/A N/A
rs4244285 24154G>A, 24154G>C, 47346080G>A, 47346080G>C, 681G>A, 681G>C, 96541616G>A, 96541616G>C, CYP2C19*2, CYP2C19:681G>A, CYP2C19:G681A, Pro227=
G > C
G > A
Synonymous
Pro227Pro
rs4986893 22948G>A, 47344874G>A, 636G>A, 96540410G>A, CYP2C19*3, CYP2C19:636G>A, CYP2C19:G636A, Trp212Ter
G > A
Stop Codon
Trp212null
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
Trade Names
  • Chloroguanide
  • Paludrine
Brand Mixture Names

PharmGKB Accession Id:
PA451124

Description

Proguanil is a prophylactic antimalarial drug, which works by stopping the malaria parasite, Plasmodium falciparum and Plasmodium vivax, from reproducing once it is in the red blood cells. It does this by inhibiting the enzyme, dihydrofolate reductase, which is involved in the reproduction of the parasite.

Source: Drug Bank

Indication

For the causal prevention and suppression of malaria caused by susceptible strains of P. falciparum and other species of Plasmodium found in some geographical areas of the world.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Proguanil inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.

Source: Drug Bank

Pharmacology

Proguanil is a biguanide derivative that is converted to an active metabolite called cycloguanil. It exerts its antimalarial action by inhibiting parasitic dihydrofolate reductase enzyme. It has causal prophylactic and suppressive activity against P. falciparum and cures the acute infection. It is also effective in suppressing the clinical attacks of vivax malaria. However it is slower compared to 4-aminoquinolines.

Source: Drug Bank

Food Interaction

Take with food.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Variably metabolized in the liver by cytochrome P450 isoenzymes to the active triazine metabolite, cycloguanil. This variable metabolism of proguanil may have profound clinical importance in poor metabolizers such as the Asian and African populations at risk for malaria infection. Prophylaxis with proguanil may not be effective in these persons because they may not achieve adequate therapeutic levels of the active compound, cycloguanil, even after multiple doses.

Source: Drug Bank

Protein Binding

Approximately 75%

Source: Drug Bank

Absorption

Rapidly and well absorbed in humans following oral doses ranging from 50 to 500 mg.

Source: Drug Bank

Half-Life

Approximately 20 hours

Source: Drug Bank

Chemical Properties

Chemical Formula

C11H16ClN5

Source: Drug Bank

Isomeric SMILES

CC(C)/N=C(\N)/N=C(\N)/Nc1ccc(cc1)Cl

Source: OpenEye

Canonical SMILES

CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1

Source: Drug Bank

Average Molecular Weight

253.731

Source: Drug Bank

Monoisotopic Molecular Weight

253.109423244

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
CYP2C19

Drug Targets

Gene Description
DHFR (source: Drug Bank)
No related drugs are available.

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
May Prevent
Contraindicated With

Publications related to proguanil: 12

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19. Pharmacogenetics and genomics. 2011. Scott Stuart A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Alteration of pharmacokinetics of proguanil in healthy volunteers following concurrent administration of efavirenz. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2010. Soyinka Julius Olugbenga, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of antimalarial drugs: effect on metabolism and transport. The Lancet infectious diseases. 2009. Kerb Reinhold, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Application of pharmacogenomics to malaria: a holistic approach for successful chemotherapy. Pharmacogenomics. 2009. Mehlotra Rajeev K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Influence of the genetic polymorphisms in the 5' flanking and exonic regions of CYP2C19 on proguanil oxidation. Drug metabolism and pharmacokinetics. 2009. Satyanarayana Chakradhara Rao Uppugunduri, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. The American journal of tropical medicine and hygiene. 2006. Hill David R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Polymorphic oxidative metabolism of proguanil in a Nigerian population. European journal of clinical pharmacology. 2002. Bolaji O O, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Association between CYP2C19 genotype and proguanil oxidative polymorphism. British journal of clinical pharmacology. 1997. Coller J K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Imipramine demethylation in vivo: impact of CYP1A2, CYP2C19, and CYP3A4. Clinical pharmacology and therapeutics. 1997. Madsen H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Proguanil metabolism in relation to S-mephenytoin oxidation in a Turkish population. British journal of clinical pharmacology. 1996. Basci N E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Evidence for the polymorphic oxidation of debrisoquine and proguanil in a Khmer (Cambodian) population. British journal of clinical pharmacology. 1995. Wanwimolruk S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Relation between chloroguanide bioactivation to cycloguanil and the genetically determined metabolism of mephenytoin in humans. Clinical pharmacology and therapeutics. 1992. Funck-Brentano C, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01131
ChEBI:
8455
KEGG Compound:
C07631
PubChem Compound:
4923
6178111
PubChem Substance:
46506228
9833
Drugs Product Database (DPD):
2043068
ChemSpider:
4754
Therapeutic Targets Database:
DAP000634

Clinical Trials

These are trials that mention proguanil and are related to either pharmacogenetics or pharmacogenomics.

Common Searches

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.