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Identification
NameAmprenavir
Accession NumberDB00701  (APRD00605)
Typesmall molecule
Groupsapproved
Description

Amprenavir is a protease inhibitor used to treat HIV infection.

Structure
Thumb
Synonyms
SynonymLanguageCode
(3S)-Tetrahydro-3-furanyl ((1S,2R)-3-(((4-aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)carbamateNot AvailableNot Available
AgeneraseNot AvailableNot Available
AmprenavirGerman/SpanishINN
AmprénavirFrenchINN
AmprenavirumLatinINN
SaltsNot Available
Brand names
NameCompany
AgemeraseGlaxoSmithKline
AgeneraseGlaxoSmithKline
ProzeiKissei Pharmaceuticals Co., Ltd.
Brand mixturesNot Available
Categories
CAS number161814-49-9
WeightAverage: 505.627
Monoisotopic: 505.224656557
Chemical FormulaC25H35N3O6S
InChI KeyYMARZQAQMVYCKC-OEMFJLHTSA-N
InChI
InChI=1S/C25H35N3O6S/c1-18(2)15-28(35(31,32)22-10-8-20(26)9-11-22)16-24(29)23(14-19-6-4-3-5-7-19)27-25(30)34-21-12-13-33-17-21/h3-11,18,21,23-24,29H,12-17,26H2,1-2H3,(H,27,30)/t21-,23-,24+/m0/s1
IUPAC Name
(3S)-oxolan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-1-phenylbutan-2-yl]carbamate
SMILES
CC(C)CN(C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]1CCOC1)S(=O)(=O)C1=CC=C(N)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentAminobenzenesulfonamides
Alternative parentsAmphetamines and Derivatives; Sulfonylanilines; Primary Aromatic Amines; Sulfonamides; Oxolanes; Sulfonyls; Tetrahydrofurans; Secondary Alcohols; Carbamic Acids and Derivatives; Ethers; Polyamines
Substituentsaniline; primary aromatic amine; sulfonic acid derivative; tetrahydrofuran; oxolane; sulfonyl; sulfonamide; carbamic acid derivative; secondary alcohol; polyamine; ether; alcohol; primary amine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.
Pharmacology
IndicationFor the treatment of HIV-1 infection in combination with other antiretroviral agents.
PharmacodynamicsAmprenavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Amprenavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.
Mechanism of actionAmprenavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
AbsorptionRapidly absorbed after oral administration in HIV-1-infected patients with a time to peak concentration (Tmax) typically between 1 and 2 hours after a single oral dose. The absolute oral bioavailability of amprenavir in humans has not been established.
Volume of distributionNot Available
Protein bindingVery high (90%). Amprenavir has the highest affinity for alpha(1)-acid glycoprotein.
Metabolism

Hepatic. Amprenavir is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme system. The 2 major metabolites result from oxidation of the tetrahydrofuran and aniline moieties. Glucuronide conjugates of oxidized metabolites have been identified as minor metabolites in urine and feces.

Route of eliminationNot Available
Half life7.1-10.6 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Human Immunodeficiency Virus
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9132
Blood Brain Barrier - 0.5886
Caco-2 permeable + 0.8866
P-glycoprotein substrate Substrate 0.7175
P-glycoprotein inhibitor I Inhibitor 0.7973
P-glycoprotein inhibitor II Non-inhibitor 0.8383
Renal organic cation transporter Non-inhibitor 0.8815
CYP450 2C9 substrate Non-substrate 0.5
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Substrate 0.6176
CYP450 1A2 substrate Non-inhibitor 0.7641
CYP450 2C9 substrate Non-inhibitor 0.6591
CYP450 2D6 substrate Non-inhibitor 0.8821
CYP450 2C19 substrate Non-inhibitor 0.6641
CYP450 3A4 substrate Inhibitor 0.6185
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7229
Ames test Non AMES toxic 0.6097
Carcinogenicity Non-carcinogens 0.8218
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.4787 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9884
hERG inhibition (predictor II) Non-inhibitor 0.8733
Pharmacoeconomics
Manufacturers
  • Glaxosmithkline
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
LiquidOral
Prices
Unit descriptionCostUnit
Agenerase 50 mg capsule0.65USDcapsule
Agenerase 15 mg/ml Solution0.21USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States67306791997-11-112017-11-11
United States55853971993-12-172013-12-17
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility4.91e-02 g/lALOGPS
logP1.85ALOGPS
logP2.43ChemAxon
logS-4ALOGPS
pKa (strongest acidic)13.61ChemAxon
pKa (strongest basic)2.39ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count6ChemAxon
hydrogen donor count3ChemAxon
polar surface area131.19ChemAxon
rotatable bond count11ChemAxon
refractivity134.08ChemAxon
polarizability53.6ChemAxon
number of rings3ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US5585397
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00894
KEGG CompoundC08086
PubChem Compound65016
PubChem Substance46507537
ChemSpider58532
BindingDB577
ChEBI2684
ChEMBLCHEMBL116
Therapeutic Targets DatabaseDAP000170
PharmGKBPA448422
Drug Product Database2243542
RxListhttp://www.rxlist.com/cgi/generic/ampren.htm
Drugs.comhttp://www.drugs.com/cdi/amprenavir.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/age1526.shtml
WikipediaAmprenavir
ATC CodesJ05AE05J05AE07
AHFS Codes
  • 08:18.08.08
PDB Entries
FDA labelshow(120 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbacavirThe serum concentration of Abacavir may be decreased by protease inhibitors such as Amprenavir. The antiviral response should be closely monitored.
AcenocoumarolAmprenavir may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
AlprazolamAmprenavir may increase the effect and toxicity of the benzodiazepine, alprazolam.
AluminiumThe antiacid decreases the absorption of amprenavir
AmiodaroneThe protease inhibitor, amprenavir, may increase the effect and toxicity of amiodarone.
AnisindioneAmprenavir may increase the anticoagulant effect of anisindione by increasing its serum concentration.
AstemizoleIncreased risk of cardiotoxicity and arrhythmias
AtorvastatinAmprenavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
BepridilAmprenavir may increase the effect and toxicity of bepridil.
Bismuth SubsalicylateThe antiacid decreases the absorption of amprenavir
CalciumThe antiacid decreases the absorption of amprenavir
CisaprideAmprenavir may increase the effect and toxicity of cisapride.
ClorazepateAmprenavir may increase the effect and toxicity of the benzodiazepine, clorazepate.
CyclosporineThe protease inhibitor, amprenavir, may increase the effect of cyclosporine.
DelavirdineDecreased levels of delavirdine with increased levels of amprenavir
DiazepamAmprenavir may increase the effect and toxicity of the benzodiazepine, diazepam.
DicoumarolAmprenavir may increase the anticoagulant effect of dicumarol by increasing its serum concentration.
DihydroergotamineAmprenavir may increase the serum concentration of dihydroergotamine. Concomitant therapy is contraindicated.
DihydroxyaluminiumThe antiacid decreases the absorption of amprenavir
DisulfiramIncreased irsk of side effects (oral solution)
ErgotamineAmprenavir may increase the effect and toxicity of ergotamine.
Ethinyl EstradiolRitonavir could decrease the contraceptive efficacy
FentanylThe protease inhibitor, amprenavir, may increase the effect and toxicity of fentanyl.
FlurazepamAmprenavir may increase the effect and toxicity of the benzodiazepine, flurazepam.
Fusidic AcidThe protease inhibitor, amprenavir, may increase the effect and toxicity of fusidic acid.
LovastatinAmprenavir may increase the serum concentration of the lovastatin. Concomitant therapy is contraindicated.
MagnesiumThe antiacid decreases the absorption of amprenavir
Magnesium oxideThe antiacid decreases the absorption of amprenavir
MestranolRitonavir could decrease the contraceptive efficacy
MethadoneThe protease inhibitor, amprenavir, may decrease the effect of methadone.
MetronidazoleIncreased risk of side effects (oral solution)
MidazolamAmprenavir may increase the effect and toxicity of the benzodiazepine, midazolam.
PimozideAmprenavir may increase the effect and toxicity of pimozide.
RanolazineAmprenavir, a strong CYP3A4 inhibitor, may increase the serum concentratin of ranolazine by inhibiting its metabolism. Concomitant therapy is contraindicated.
RifabutinAmprenavir may increase the effect and toxicity of rifabutin.
RifampicinIn presence of rifampin anticipate decrease of amprenavir efficiency
SildenafilThe protease inhibitor, amprenavir, may increase the effect and toxicity of sildenafil.
SimvastatinAmprenavir may increase the effect and toxicity of simvastatin. Concomitant therapy is contraindicated.
St. John's WortSt. John's Wort decreases the effect of indinavir
TacrolimusThe protease inhibitor, Amprenavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Amprenavir therapy is initiated, discontinued or altered.
TadalafilAmprenavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
TamoxifenAmprenavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
TamsulosinAmprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Amprenavir is initiated, discontinued, or dose changed.
TelithromycinCo-administration may result in altered plasma concentrations of Amprenavir and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.
TemsirolimusAmprenavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
TeniposideThe strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Amprenavir is initiated, discontinued or dose changed.
TerfenadineIncreased risk of cardiotoxicity and arrhythmias
TiagabineThe strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Amprenavir is initiated, discontinued or dose changed.
TolterodineAmprenavir may decrease the metabolism and clearance of Tolterodine. Adjust the Tolterodine dose and monitor for efficacy and toxicity.
TramadolAmprenavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
TrazodoneThe protease inhibitor, Amprenavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Amprenavir is initiated, discontinued or dose changed.
TriazolamAmprenavir may increase the effect and toxicity of the benzodiazepine, triazolam.
TrimipramineThe strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Amprenavir is initiated, discontinued or dose changed.
VardenafilAmprenavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
VenlafaxineAmprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Amprenavir is initiated, discontinued, or dose changed.
VerapamilAmprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Amprenavir is initiated, discontinued or dose changed.
VinblastineAmprenavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Amprenavir is initiated, discontinued or dose changed.
VincristineAmprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Amprenavir is initiated, discontinued or dose changed.
VinorelbineAmprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Amprenavir is initiated, discontinued or dose changed.
Vitamin EIncreased serum levels of vitamin E
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of amprenavir by decreasing its metabolism. The serum concentration of voriconazole may be increased by amprenavir. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
WarfarinAmprenavir may increase the anticoagulant effect of warfarin by increasing its serum concentration.
ZolpidemAmprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if amprenavir is initiated, discontinued or dose changed.
ZonisamideAmprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if amprenavir is initiated, discontinued or dose changed.
ZopicloneAmprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if amprenavir is initiated, discontinued or dose changed.
Food Interactions
  • Avoid alcohol, especially with the oral solution since it contains propylene glycol which competes with alcohol for alcohol dehydrogenase metabolism.
  • Take with or without food, however avoid lipid-rich meals.
  • Vitamin E increases amprenavir bioavailability.

Targets

1. Protease

Kind: protein

Organism: Human immunodeficiency virus 1

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
HIV-1 Protease Q72874 Details

References:

  1. Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PBSA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2007 Sep 11;. Pubmed
  2. Dandache S, Sevigny G, Yelle J, Stranix BR, Parkin N, Schapiro JM, Wainberg MA, Wu JJ: In Vitro Antiviral Activity and Cross-Resistance Profile of PL-100, a Next Generation Protease Inhibitor of Human Immunodeficiency Virus Type 1. Antimicrob Agents Chemother. 2007 Jul 16;. Pubmed
  3. Sadler BM, Hanson CD, Chittick GE, Symonds WT, Roskell NS: Safety and pharmacokinetics of amprenavir (141W94), a human immunodeficiency virus (HIV) type 1 protease inhibitor, following oral administration of single doses to HIV-infected adults. Antimicrob Agents Chemother. 1999 Jul;43(7):1686-92. Pubmed
  4. Amprenavir: a new HIV protease inhibitor. Med Lett Drugs Ther. 1999 Jul 16;41(1057):64-6. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. 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. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

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. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

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. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

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. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor inducer

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Perloff MD, von Moltke LL, Fahey JM, Daily JP, Greenblatt DJ: Induction of P-glycoprotein expression by HIV protease inhibitors in cell culture. AIDS. 2000 Jun 16;14(9):1287-9. Pubmed
  2. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed

2. Multidrug resistance-associated protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 1 P33527 Details

References:

  1. Olson DP, Scadden DT, D’Aquila RT, De Pasquale MP: The protease inhibitor ritonavir inhibits the functional activity of the multidrug resistance related-protein 1 (MRP-1). AIDS. 2002 Sep 6;16(13):1743-7. Pubmed

Comments
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Drug created on June 13, 2005 07:24 / Updated on December 04, 2013 16:17