Identification

Name
Proguanil
Accession Number
DB01131  (APRD00188)
Type
Small Molecule
Groups
Approved
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.

Structure
Thumb
Synonyms
  • N-(4-Chlorophenyl)-n'-(isopropyl)-imidodicarbonimidic diamide
  • 1-(P-Chlorophenyl)-5-isopropylbiguanide
  • Chlorguanide
  • Chloroguanide
  • N-(4-Chlorophenyl)-n'-(isopropyl)-imidodicarbonimidic diamide
  • Proguanilo
  • Proguanilum
Product Ingredients
IngredientUNIICASInChI Key
Proguanil hydrochlorideR71Y86M0WT637-32-1SARMGXPVOFNNNG-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Paludrine Tab 0.1gmTablet100 mgOralAyerst Laboratories1974-12-311997-08-15Canada
Paludrine Tab 100mgTablet100 mgOralWyeth Ayerst Canada Inc.1996-10-252005-02-28Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Atovaquone and Proguanil HClProguanil hydrochloride (100 mg/1) + Atovaquone (250 mg/1)Tablet, film coatedOralA-S Medication Solutions2012-07-27Not applicableUs
Atovaquone and Proguanil HClProguanil hydrochloride (100 mg/1) + Atovaquone (250 mg/1)Tablet, film coatedOralbryant ranch prepack2012-07-27Not applicableUs
Atovaquone and Proguanil HClProguanil hydrochloride (100 mg/1) + Atovaquone (250 mg/1)Tablet, film coatedOralPd Rx Pharmaceuticals, Inc.2012-07-27Not applicableUs
Atovaquone and Proguanil HClProguanil hydrochloride (100 mg/1) + Atovaquone (250 mg/1)Tablet, film coatedOralPrasco, Laboratories2012-07-27Not applicableUs
Atovaquone and Proguanil HydrochlorideProguanil hydrochloride (25 mg/1) + Atovaquone (62.5 mg/1)Tablet, film coatedOralMylan Pharmaceuticals Inc.2014-05-28Not applicableUs
Atovaquone and Proguanil HydrochlorideProguanil hydrochloride (100 mg/1) + Atovaquone (250 mg/1)Tablet, film coatedOralClinical Solutions Wholsesale2011-08-182017-06-22Us58118 040420180913 8702 jc0y6p
Atovaquone and Proguanil HydrochlorideProguanil hydrochloride (100 mg/1) + Atovaquone (250 mg/1)TabletOralRebel Distributors2011-08-18Not applicableUs
Atovaquone and Proguanil HydrochlorideProguanil hydrochloride (100 mg/1) + Atovaquone (250 mg/1)Tablet, film coatedOralDispensing Solutions, Inc.2011-08-18Not applicableUs68258 110420180907 15195 1u4lcab
Atovaquone and Proguanil HydrochlorideProguanil hydrochloride (100 mg/1) + Atovaquone (250 mg/1)Tablet, film coatedOralGlenmark Pharmaceuticals Inc.,Usa2011-09-15Not applicableUs68462 0404 67 nlmimage10 cc39e66f
Atovaquone and Proguanil HydrochlorideProguanil hydrochloride (100 mg/1) + Atovaquone (250 mg/1)Tablet, film coatedOralSt. Mary's Medical Park Pharmacy2011-08-18Not applicableUs
International/Other Brands
Chloroguanide / Paludrine
Categories
UNII
S61K3P7B2V
CAS number
500-92-5
Weight
Average: 253.731
Monoisotopic: 253.109423244
Chemical Formula
C11H16ClN5
InChI Key
SSOLNOMRVKKSON-UHFFFAOYSA-N
InChI
InChI=1S/C11H16ClN5/c1-7(2)15-10(13)17-11(14)16-9-5-3-8(12)4-6-9/h3-7H,1-2H3,(H5,13,14,15,16,17)
IUPAC Name
(E)-1-({amino[(4-chlorophenyl)amino]methylidene}amino)-N'-(propan-2-yl)methenimidamide
SMILES
CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1

Pharmacology

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.

Associated Conditions
Pharmacodynamics

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.

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.

TargetActionsOrganism
ADihydrofolate reductase
inhibitor
Human
UBifunctional dihydrofolate reductase-thymidylate synthase
inhibitor
Plasmodium falciparum (isolate K1 / Thailand)
Absorption

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

Volume of distribution
Not Available
Protein binding

Approximately 75%

Metabolism

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.

Route of elimination
Not Available
Half life

Approximately 20 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Plasmodium
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2C19CYP2C19*2(A;A)A Allele, homozygoteEffect Directly StudiedPatients with this genotype have reduced metabolism of proguanil.Details
Cytochrome P450 2C19CYP2C19*3(A;A)A Allele, homozygoteEffect Directly StudiedPatients with this genotype have reduced metabolism of proguanil.Details
Cytochrome P450 2C19CYP2C19*2ANot Available681G>AEffect InferredPoor metabolizer, lower dose requirementDetails
Cytochrome P450 2C19CYP2C19*2BNot Available681G>AEffect InferredPoor metabolizer, lower dose requirementDetails
Cytochrome P450 2C19CYP2C19*4Not Available1A>GEffect InferredPoor metabolizer, lower dose requirementDetails
Cytochrome P450 2C19CYP2C19*5Not Available1297C>TEffect InferredPoor metabolizer, lower dose requirementDetails
Cytochrome P450 2C19CYP2C19*6Not Available395G>AEffect InferredPoor metabolizer, lower dose requirementDetails
Cytochrome P450 2C19CYP2C19*7Not Available19294T>AEffect InferredPoor metabolizer, lower dose requirementDetails
Cytochrome P450 2C19CYP2C19*22Not Available557G>C / 991A>GEffect InferredPoor metabolizer, lower dose requirementDetails
Cytochrome P450 2C19CYP2C19*24Not Available99C>T / 991A>G  … show all Effect InferredPoor metabolizer, lower dose requirementDetails
Cytochrome P450 2C19CYP2C19*35Not Available12662A>GEffect InferredPoor metabolizer, lower dose requirementDetails

Interactions

Drug Interactions
DrugInteraction
(6R)-Folinic acidThe therapeutic efficacy of Proguanil can be decreased when used in combination with (6R)-Folinic acid.
(6S)-5,6,7,8-tetrahydrofolateThe therapeutic efficacy of Proguanil can be decreased when used in combination with (6S)-5,6,7,8-tetrahydrofolate.
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Proguanil.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Proguanil.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Proguanil.
AbirateroneThe metabolism of Proguanil can be decreased when combined with Abiraterone.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Proguanil.
AceclofenacThe metabolism of Aceclofenac can be decreased when combined with Proguanil.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Proguanil.
AcepromazineThe risk or severity of QTc prolongation can be increased when Proguanil is combined with Acepromazine.
Food Interactions
  • Take with food.

References

Synthesis Reference

Dhananjay Govind Sathe, Harish Kashinath Mondkar, Tanaji Shamrao Jadhav, Nitin Nivrutti Hagavane, "Process of Preparation of Proguanil." U.S. Patent US20110263901, issued October 27, 2011.

US20110263901
General References
Not Available
External Links
Human Metabolome Database
HMDB0015263
KEGG Compound
C07631
PubChem Compound
4923
PubChem Substance
46506228
ChemSpider
4754
ChEBI
8455
ChEMBL
CHEMBL1377
Therapeutic Targets Database
DAP000634
PharmGKB
PA451124
Drugs.com
Drugs.com Drug Page
Wikipedia
Proguanil
ATC Codes
P01BB51 — Proguanil, combinationsP01BB01 — Proguanil
AHFS Codes
  • 08:30.08 — Antimalarials

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingPreventionPlasmodium Infections1
1CompletedBasic ScienceCYP2C19 Genotypes1
1CompletedPreventionMalaria caused by Plasmodium falciparum1
1, 2CompletedOtherPlasmodium Infections1
1, 2CompletedPreventionPlasmodium Infections / Sickle Cell Crisis1
2CompletedPreventionPlasmodium Infections1
2RecruitingTreatmentPlasmodium Infections1
2, 3CompletedTreatmentMalaria caused by Plasmodium falciparum1
4CompletedNot AvailablePlasmodium Infections1
4CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Plasmodium Infections1
4CompletedTreatmentFalciparum / Plasmodium Infections1
4CompletedTreatmentPlasmodium Infections1
4RecruitingPreventionMalaria caused by Plasmodium falciparum1
4RecruitingPreventionRabies1
4RecruitingTreatmentPlasmodium Falciparum Malaria (Drug Resistant)1
Not AvailableCompletedBasic ScienceMalaria caused by Plasmodium falciparum1
Not AvailableCompletedBasic SciencePlasmodium Falciparum Malaria2
Not AvailableCompletedBasic SciencePlasmodium Falciparum / Plasmodium Infections1
Not AvailableCompletedBasic SciencePlasmodium Infections1
Not AvailableCompletedPreventionPlasmodium Infections1
Not AvailableNot Yet RecruitingOtherControlled Human Malaria Infection / Gametocytes / Malaria caused by Plasmodium falciparum / Transmission1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • A-S Medication Solutions LLC
  • GlaxoSmithKline Inc.
  • St Mary's Medical Park Pharmacy
Dosage forms
FormRouteStrength
Tablet, film coatedOral
TabletOral
TabletOral100 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)129 °CPhysProp
water solubility156 mg/LNot Available
logP2.53SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.286 mg/mLALOGPS
logP1.9ALOGPS
logP1.89ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)19.77ChemAxon
pKa (Strongest Basic)10.12ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area88.79 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity71.07 m3·mol-1ChemAxon
Polarizability26.84 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9544
Blood Brain Barrier+0.728
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.7
P-glycoprotein inhibitor INon-inhibitor0.9482
P-glycoprotein inhibitor IINon-inhibitor0.8511
Renal organic cation transporterNon-inhibitor0.7381
CYP450 2C9 substrateNon-substrate0.7646
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateNon-substrate0.6085
CYP450 1A2 substrateInhibitor0.8751
CYP450 2C9 inhibitorNon-inhibitor0.9591
CYP450 2D6 inhibitorInhibitor0.6507
CYP450 2C19 inhibitorNon-inhibitor0.9405
CYP450 3A4 inhibitorNon-inhibitor0.9109
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8774
Ames testNon AMES toxic0.5887
CarcinogenicityNon-carcinogens0.616
BiodegradationNot ready biodegradable0.9939
Rat acute toxicity2.6787 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9701
hERG inhibition (predictor II)Non-inhibitor0.9265
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 1-arylbiguanides. These are organonitrogen compounds containing a biguanide that is N-arylsubstituted at only the 1-position.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Guanidines
Direct Parent
1-arylbiguanides
Alternative Parents
Chlorobenzenes / Aryl chlorides / Carboximidamides / Organopnictogen compounds / Organochlorides / Imines / Hydrocarbon derivatives
Substituents
1-arylbiguanide / Halobenzene / Chlorobenzene / Benzenoid / Monocyclic benzene moiety / Aryl halide / Aryl chloride / Carboximidamide / Organopnictogen compound / Hydrocarbon derivative
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monochlorobenzenes, biguanides (CHEBI:8455)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Nadph binding
Specific Function
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA pre...
Gene Name
DHFR
Uniprot ID
P00374
Uniprot Name
Dihydrofolate reductase
Molecular Weight
21452.61 Da
References
  1. Kaneko A, Bergqvist Y, Takechi M, Kalkoa M, Kaneko O, Kobayakawa T, Ishizaki T, Bjorkman A: Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil. J Infect Dis. 1999 Apr;179(4):974-9. [PubMed:10068594]
  2. Vasconcelos KF, Plowe CV, Fontes CJ, Kyle D, Wirth DF, Pereira da Silva LH, Zalis MG: Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase of isolates from the Amazon region of Brazil. Mem Inst Oswaldo Cruz. 2000 Sep-Oct;95(5):721-8. [PubMed:10998224]
  3. Tahar R, de Pecoulas PE, Basco LK, Chiadmi M, Mazabraud A: Kinetic properties of dihydrofolate reductase from wild-type and mutant Plasmodium vivax expressed in Escherichia coli. Mol Biochem Parasitol. 2001 Apr 6;113(2):241-9. [PubMed:11295178]
  4. Durand R, Jafari S, Bouchaud O, Ralaimazava P, Keundjian A, Le Bras J: Plasmodium falciparum: pfcrt and DHFR mutations are associated with failure of chloroquine plus proguanil prophylaxis in travelers. J Infect Dis. 2001 Dec 15;184(12):1633-4. [PubMed:11740746]
  5. Le Bras J, Durand R: The mechanisms of resistance to antimalarial drugs in Plasmodium falciparum. Fundam Clin Pharmacol. 2003 Apr;17(2):147-53. [PubMed:12667224]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Plasmodium falciparum (isolate K1 / Thailand)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Thymidylate synthase activity
Specific Function
Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and f...
Gene Name
Not Available
Uniprot ID
P13922
Uniprot Name
Bifunctional dihydrofolate reductase-thymidylate synthase
Molecular Weight
71816.775 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Lu AH, Shu Y, Huang SL, Wang W, Ou-Yang DS, Zhou HH: In vitro proguanil activation to cycloguanil is mediated by CYP2C19 and CYP3A4 in adult Chinese liver microsomes. Acta Pharmacol Sin. 2000 Aug;21(8):747-52. [PubMed:11501186]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Bapiro TE, Egnell AC, Hasler JA, Masimirembwa CM: Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5. [PubMed:11124226]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on December 10, 2018 06:10