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Identification
NameProcainamide
Accession NumberDB01035  (APRD00509)
Typesmall molecule
Groupsapproved
Description

A derivative of procaine with less CNS action. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
p-Amino-N-(2-diethylaminoethyl)benzamideNot AvailableNot Available
p-Aminobenzoic diethylaminoethylamideNot AvailableNot Available
Salts
Name/CAS Structure Properties
Procainamide Hydrochloride
Thumb
  • InChI Key: ABTXGJFUQRCPNH-UHFFFAOYSA-N
  • Monoisotopic Mass: 271.145140048
  • Average Mass: 271.786
DBSALT000724
Brand names
NameCompany
BiocorylNot Available
ProcanNot Available
ProcanbidNot Available
ProcapanNot Available
PronestylNot Available
Brand mixturesNot Available
Categories
CAS number51-06-9
WeightAverage: 235.3253
Monoisotopic: 235.168462309
Chemical FormulaC13H21N3O
InChI KeyREQCZEXYDRLIBE-UHFFFAOYSA-N
InChI
InChI=1S/C13H21N3O/c1-3-16(4-2)10-9-15-13(17)11-5-7-12(14)8-6-11/h5-8H,3-4,9-10,14H2,1-2H3,(H,15,17)
IUPAC Name
4-amino-N-[2-(diethylamino)ethyl]benzamide
SMILES
CCN(CC)CCNC(=O)C1=CC=C(N)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzamides
Direct parentAminobenzamides
Alternative parentsBenzoyl Derivatives; Anilines; Primary Aromatic Amines; Tertiary Amines; Secondary Carboxylic Acid Amides; Carboxylic Acids; Enolates; Polyamines
Substituentsbenzoyl; aniline; primary aromatic amine; carboxamide group; tertiary amine; secondary carboxylic acid amide; polyamine; enolate; carboxylic acid derivative; carboxylic acid; primary amine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the aminobenzamides. These are organic compounds containing a benzamide moiety with an amine group attached to the benzene ring.
Pharmacology
IndicationFor the treatment of life-threatening ventricular arrhythmias.
PharmacodynamicsProcainamide is an agent indicated for production of local or regional anesthesia and in the treatment of ventricular tachycardia occurring during cardiac manipulation, such as surgery or catheterization, or which may occur during acute myocardial infarction, digitalis toxicity, or other cardiac diseases. The mode of action of the antiarrhythmic effect of Procainamide appears to be similar to that of procaine and quinidine. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole. The sinoatrial node is, however, unaffected.
Mechanism of actionProcainamide is sodium channel blocker. It stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action.
Absorption75 to 95%
Volume of distribution
  • 2 L/kg
Protein binding15 to 20%
Metabolism

Hepatic

SubstrateEnzymesProduct
Procainamide
N-Acetyl-3-hydroxyprocainamideDetails
Route of eliminationTrace amounts may be excreted in the urine as free and conjugated p-aminobenzoic acid, 30 to 60 percent as unchanged PA, and 6 to 52 percent as the NAPA derivative.
Half life~2.5-4.5 hours
ClearanceNot Available
ToxicityLD50=95 mg/kg (rat, IV); LD50=312 mg/kg (mouse, oral); LD50=103 mg/kg (mouse, IV); LD50=250 mg/kg (rabbit, IV)
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Procainamide (Antiarrhythmic) Action PathwayDrug actionSMP00324
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9561
Blood Brain Barrier + 0.9675
Caco-2 permeable + 0.666
P-glycoprotein substrate Substrate 0.7739
P-glycoprotein inhibitor I Non-inhibitor 0.9452
P-glycoprotein inhibitor II Non-inhibitor 0.9654
Renal organic cation transporter Non-inhibitor 0.7526
CYP450 2C9 substrate Non-substrate 0.8624
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Non-substrate 0.6306
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.9384
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9606
CYP450 3A4 substrate Non-inhibitor 0.9238
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8833
Ames test Non AMES toxic 0.7822
Carcinogenicity Non-carcinogens 0.5352
Biodegradation Not ready biodegradable 0.9855
Rat acute toxicity 2.1133 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9454
hERG inhibition (predictor II) Non-inhibitor 0.648
Pharmacoeconomics
Manufacturers
  • Parke davis div warner lambert co
  • Panray corp sub ormont drug and chemical co inc
  • Apothecon inc div bristol myers squibb
  • Parkedale pharmaceuticals inc
  • King pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
SolutionIntramuscular
Tablet, extended releaseOral
Prices
Unit descriptionCostUnit
Procainamide 500 mg/ml vial6.45USDml
Procainamide 100 mg/ml vial1.29USDml
Procan Sr 750 mg Sustained-Release Tablet0.91USDtablet
Procan Sr 500 mg Sustained-Release Tablet0.56USDtablet
Procan Sr 250 mg Sustained-Release Tablet0.4USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States56562961994-08-122014-08-12
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point165-169 °CNot Available
water solubility5050 mg/LNot Available
logP0.88HANSCH,C ET AL. (1995)
pKa9.32SANGSTER (1994)
Predicted Properties
PropertyValueSource
water solubility3.02e+00 g/lALOGPS
logP1.42ALOGPS
logP0.95ChemAxon
logS-1.9ALOGPS
pKa (strongest acidic)15.75ChemAxon
pKa (strongest basic)9.04ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count2ChemAxon
polar surface area58.36ChemAxon
rotatable bond count6ChemAxon
refractivity72.25ChemAxon
polarizability27.69ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Victor Chu, Zhu Teng, Steve Goss, Ronald Edwards, Kelle Garvey, Timothy Gorzynski, William Bedzyk, “Synthesis and application of procainamide analogs for use in an immunoassay.” U.S. Patent US20050227288, issued October 13, 2005.

US20050227288
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07401
PubChem Compound4913
PubChem Substance46507313
ChemSpider4744
ChEBI8428
ChEMBLCHEMBL640
Therapeutic Targets DatabaseDAP000516
PharmGKBPA451108
Drug Product Database713341
RxListhttp://www.rxlist.com/cgi/generic3/procain.htm
Drugs.comhttp://www.drugs.com/cdi/procainamide.html
WikipediaProcainamide
ATC CodesNot Available
AHFS Codes
  • 24:04.04.04
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(72 KB)
Interactions
Drug Interactions
Drug
AmiodaroneAmiodarone may increase serum levels and toxicity of procainamide.
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
CimetidineThe histamine H2-receptor antagonist, cimetidine, may increase the effect of procainamide.
CiprofloxacinCiprofloxacin may increase the effect of procainamide.
CisaprideIncreased risk of cardiotoxicity and arrhythmias
Dihydroquinidine barbiturateQuinidine increases the effect of procainamide
DonepezilPossible antagonism of action
FingolimodPharmacodynamic synergist. Contraindicated. Increased risk of bradycardia, AV block, and torsade de pointes.
GalantaminePossible antagonism of action
LevofloxacinLevofloxacin may increase the effect of procainamide.
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MesoridazineIncreased risk of cardiotoxicity and arrhythmias
OfloxacinOfloxacin may increase the effect of procainamide.
QuinidineQuinidine increases the effect of procainamide
Quinidine barbiturateQuinidine increases the effect of procainamide
RanitidineThe histamine H2-receptor antagonist, ranitidine, may increase the effect of procainamide.
RanolazinePossible additive effect on QT prolongation
RivastigminePossible antagonism of action
TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
TelavancinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
TerbinafineTerbinafine may reduce the metabolism and clearance of Procainamide. Consider alternate therapy or monitor for therapeutic/adverse effects of Procainamide if Terbinafine is initiated, discontinued or dose changed.
TerfenadineIncreased risk of cardiotoxicity and arrhythmias
ThioridazineIncreased risk of cardiotoxicity and arrhythmias
ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
ToremifeneAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
TrimethoprimTrimethoprim may reduce the clearance of Procainamide. Alternative treatments should be considered. If Trimethoprim is initiated or the dose is increased, monitor for increased toxicity of Procainamide (e.g. QTc intervals, EKG, serum drug concentrations). If Trimethoprim is discontinued or the dose decreased, monitor for reduced effects of Procainamide.
TrimipramineAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
VardenafilIncreased risk of cardiotoxicity and arrhythmias
VoriconazoleAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
ZuclopenthixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Zuclopenthixol acetateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Zuclopenthixol decanoateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.

Targets

1. Sodium channel protein type 5 subunit alpha

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Sodium channel protein type 5 subunit alpha Q14524 Details

References:

  1. Weiss R, Barmada MM, Nguyen T, Seibel JS, Cavlovich D, Kornblit CA, Angelilli A, Villanueva F, McNamara DM, London B: Clinical and molecular heterogeneity in the Brugada syndrome: a novel gene locus on chromosome 3. Circulation. 2002 Feb 12;105(6):707-13. Pubmed
  2. Brugada R, Brugada J, Antzelevitch C, Kirsch GE, Potenza D, Towbin JA, Brugada P: Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation. 2000 Feb 8;101(5):510-5. Pubmed
  3. Chen SM, Kuo CT, Lin KH, Chiang FT: Brugada syndrome without mutation of the cardiac sodium channel gene in a Taiwanese patient. J Formos Med Assoc. 2000 Nov;99(11):860-2. Pubmed
  4. Brugada J, Brugada R, Brugada P: [Brugada syndrome] Arch Mal Coeur Vaiss. 1999 Jul;92(7):847-50. Pubmed
  5. Brugada J, Brugada P, Brugada R: The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death—the Brugada syndrome. Europace. 1999 Jul;1(3):156-66. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. DNA (cytosine-5)-methyltransferase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other

Components

Name UniProt ID Details
DNA (cytosine-5)-methyltransferase 1 P26358 Details

References:

  1. Oelke K, Lu Q, Richardson D, Wu A, Deng C, Hanash S, Richardson B: Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors. Arthritis Rheum. 2004 Jun;50(6):1850-60. Pubmed
  2. Januchowski R, Jagodzinski PP: Effect of 5-azacytidine and procainamide on CD3-zeta chain expression in Jurkat T cells. Biomed Pharmacother. 2005 Apr;59(3):122-6. Pubmed
  3. Lee BH, Yegnasubramanian S, Lin X, Nelson WG: Procainamide is a specific inhibitor of DNA methyltransferase 1. J Biol Chem. 2005 Dec 9;280(49):40749-56. Epub 2005 Oct 17. Pubmed
  4. Scheinbart LS, Johnson MA, Gross LA, Edelstein SR, Richardson BC: Procainamide inhibits DNA methyltransferase in a human T cell line. J Rheumatol. 1991 Apr;18(4):530-4. Pubmed

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Lessard E, Hamelin BA, Labbe L, O’Hara G, Belanger PM, Turgeon J: Involvement of CYP2D6 activity in the N-oxidation of procainamide in man. Pharmacogenetics. 1999 Dec;9(6):683-96. Pubmed
  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. Epub 2009 Nov 24. Pubmed

2. Cholinesterase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cholinesterase P06276 Details

References:

  1. Bailey DN: Amitriptyline and procainamide inhibition of cocaine and cocaethylene degradation in human serum in vitro. J Anal Toxicol. 1999 Mar-Apr;23(2):99-102. Pubmed
  2. Page JD, Wilson IB, Silman I: Butyrylcholinesterase: inhibition by arsenite, fluoride, and other ligands, cooperativity in binding. Mol Pharmacol. 1985 Apr;27(4):437-43. Pubmed

Transporters

1. Solute carrier family 22 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 2 O15244 Details

References:

  1. Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. Pubmed
  2. Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H: Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81. Pubmed
  3. Kakehi M, Koyabu N, Nakamura T, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Biochem Biophys Res Commun. 2002 Aug 23;296(3):644-50. Pubmed
  4. Arndt P, Volk C, Gorboulev V, Budiman T, Popp C, Ulzheimer-Teuber I, Akhoundova A, Koppatz S, Bamberg E, Nagel G, Koepsell H: Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. Am J Physiol Renal Physiol. 2001 Sep;281(3):F454-68. Pubmed
  5. Goralski KB, Lou G, Prowse MT, Gorboulev V, Volk C, Koepsell H, Sitar DS: The cation transporters rOCT1 and rOCT2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules. J Pharmacol Exp Ther. 2002 Dec;303(3):959-68. Pubmed
  6. Ishiguro N, Saito A, Yokoyama K, Morikawa M, Igarashi T, Tamai I: Transport of the dopamine D2 agonist pramipexole by rat organic cation transporters OCT1 and OCT2 in kidney. Drug Metab Dispos. 2005 Apr;33(4):495-9. Epub 2005 Jan 7. Pubmed
  7. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. Pubmed

2. Solute carrier family 22 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 1 O15245 Details

References:

  1. Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. Pubmed
  2. Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, Giacomini KM: Cloning and functional expression of a human liver organic cation transporter. Mol Pharmacol. 1997 Jun;51(6):913-21. Pubmed
  3. Zhang L, Schaner ME, Giacomini KM: Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998 Jul;286(1):354-61. Pubmed
  4. Kakehi M, Koyabu N, Nakamura T, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Biochem Biophys Res Commun. 2002 Aug 23;296(3):644-50. Pubmed
  5. Green RM, Lo K, Sterritt C, Beier DR: Cloning and functional expression of a mouse liver organic cation transporter. Hepatology. 1999 May;29(5):1556-62. Pubmed
  6. Zhang L, Dresser MJ, Chun JK, Babbitt PC, Giacomini KM: Cloning and functional characterization of a rat renal organic cation transporter isoform (rOCT1A). J Biol Chem. 1997 Jun 27;272(26):16548-54. Pubmed
  7. Goralski KB, Lou G, Prowse MT, Gorboulev V, Volk C, Koepsell H, Sitar DS: The cation transporters rOCT1 and rOCT2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules. J Pharmacol Exp Ther. 2002 Dec;303(3):959-68. Pubmed
  8. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. Pubmed
  9. Grundemann D, Gorboulev V, Gambaryan S, Veyhl M, Koepsell H: Drug excretion mediated by a new prototype of polyspecific transporter. Nature. 1994 Dec 8;372(6506):549-52. Pubmed
  10. Ishiguro N, Saito A, Yokoyama K, Morikawa M, Igarashi T, Tamai I: Transport of the dopamine D2 agonist pramipexole by rat organic cation transporters OCT1 and OCT2 in kidney. Drug Metab Dispos. 2005 Apr;33(4):495-9. Epub 2005 Jan 7. Pubmed

3. Solute carrier family 22 member 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 3 O75751 Details

References:

  1. Wu X, Huang W, Ganapathy ME, Wang H, Kekuda R, Conway SJ, Leibach FH, Ganapathy V: Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol. 2000 Sep;279(3):F449-58. Pubmed

4. Solute carrier family 22 member 5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 5 O76082 Details

References:

  1. Wu X, Prasad PD, Leibach FH, Ganapathy V: cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun. 1998 May 29;246(3):589-95. Pubmed
  2. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. Pubmed
  3. Ohashi R, Tamai I, Nezu Ji J, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A: Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol. 2001 Feb;59(2):358-66. Pubmed
  4. Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V: Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999 Sep;290(3):1482-92. Pubmed

5. Solute carrier family 22 member 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 4 Q9H015 Details

References:

  1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. Pubmed
  2. Wu X, George RL, Huang W, Wang H, Conway SJ, Leibach FH, Ganapathy V: Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim Biophys Acta. 2000 Jun 1;1466(1-2):315-27. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13