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Identification
NameRetapamulin
Accession NumberDB01256
TypeSmall Molecule
GroupsApproved
Description

Retapamulin is a topical antibiotic developed by GlaxoSmithKline. It was approved by the United States Food and Drug Administration in April 2007 for the treatment of bacterial skin infections such as impetigo. It is marketed as an ointment under the name brand Altabax.

Structure
Thumb
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
AltabaxGlaxo
Brand mixturesNot Available
Categories
CAS number224452-66-8
WeightAverage: 517.763
Monoisotopic: 517.322579687
Chemical FormulaC30H47NO4S
InChI KeySTZYTFJPGGDRJD-FJJJPKKESA-N
InChI
InChI=1S/C30H47NO4S/c1-7-28(4)16-24(35-25(33)17-36-22-14-20-8-9-21(15-22)31(20)6)29(5)18(2)10-12-30(19(3)27(28)34)13-11-23(32)26(29)30/h7,18-22,24,26-27,34H,1,8-17H2,2-6H3/t18-,19+,20-,21+,22?,24-,26+,27+,28-,29+,30+/m1/s1
IUPAC Name
(1S,2R,3S,4S,6R,7R,8R,14R)-4-ethenyl-3-hydroxy-2,4,7,14-tetramethyl-9-oxotricyclo[5.4.3.0^{1,8}]tetradecan-6-yl 2-{[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl]sulfanyl}acetate
SMILES
C[C@@H]1CC[C@@]23CCC(=O)[C@H]2[C@]1(C)[C@@H](C[C@@](C)(C=C)[C@@H](O)[C@@H]3C)OC(=O)CSC1C[C@@H]2CC[C@H](C1)N2C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassPrenol Lipids
SubclassTerpene Lactones
Direct parentPleuromutilin and Derivatives
Alternative parentsDiterpenes; Tropanes; Heterocyclic Fatty Acids; Thia Fatty Acids; Unsaturated Fatty Acids; Piperidines; Pyrrolidines; Cyclic Alcohols and Derivatives; Tertiary Amines; Ketones; Secondary Alcohols; Carboxylic Acid Esters; Enolates; Ethers; Thioethers; Polyamines
Substituentsditerpene; tropane; piperidine; pyrrolidine; cyclic alcohol; secondary alcohol; tertiary amine; ketone; carboxylic acid ester; enolate; polyamine; carboxylic acid derivative; thioether; ether; alcohol; organonitrogen compound; amine; carbonyl group
Classification descriptionThis compound belongs to the pleuromutilin and derivatives. These are mutilins with an hydroxyacetate derivative attached to the C8 carbon atom of the cyclopenta[8]annulene moiety.
Pharmacology
IndicationFor use in adults and pediatric patients aged 9 months and older for the topical treatment of impetigo (up to 100 cm2 in total area in adults or 2% total body surface area in pediatric patients aged 9 months or older) due to Staphylococcus aureus (methicillin-susceptible isolates only) or Streptococcus pyogenes.
PharmacodynamicsRetapamulin is a semisynthetic pleuromutilin antibiotic. This drug is usually bacteriostatic in action, but may become bactericidal at highed concentrations (when MBC is 1000 times higher than MIC). Retapamulin acts by selectively inhibiting the initiation of protein synthesis in bacteria at the level of bacterial 50S ribosome.
Mechanism of actionRetapamulin is a bacterial protein synthesis inhibitor belonging to a class of compounds called pleuromutilins. These compounds inhibit the initiation of protein synthesis by binding to a specific site on the 50S subunit of bacterial ribosome (domain V of 23S rRNA). This binding site involves ribosomal protein L3 and is in the region of the ribosomal P site and peptidyl transferase center. By virtue of binding to this site, pleuromutilins inhibit peptidyl transfer, block P-site interactions, and prevent the normal formation of active 50S ribosomal subunits.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingRetapamulin is approximately 94% bound to human plasma proteins, and the protein binding is independent of concentration.
Metabolism

In vitro studies with human liver microsomes demonstrated that retapamulin is extensively metabolized to numerous metabolites, of which the predominant routes of metabolism were mono-oxygenation and N-demethylation. The major enzyme responsible for metabolism of retapamulin in human liver microsomes was cytochrome P450 3A4 (CYP3A4).

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Bacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.5359
Blood Brain Barrier + 0.8647
Caco-2 permeable + 0.5282
P-glycoprotein substrate Substrate 0.6692
P-glycoprotein inhibitor I Inhibitor 0.881
P-glycoprotein inhibitor II Inhibitor 0.7432
Renal organic cation transporter Inhibitor 0.5618
CYP450 2C9 substrate Non-substrate 0.7457
CYP450 2D6 substrate Non-substrate 0.7732
CYP450 3A4 substrate Substrate 0.7848
CYP450 1A2 substrate Non-inhibitor 0.7993
CYP450 2C9 substrate Non-inhibitor 0.7935
CYP450 2D6 substrate Non-inhibitor 0.882
CYP450 2C19 substrate Non-inhibitor 0.8004
CYP450 3A4 substrate Non-inhibitor 0.5938
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8717
Ames test Non AMES toxic 0.7256
Carcinogenicity Non-carcinogens 0.9557
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.7920 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9704
hERG inhibition (predictor II) Non-inhibitor 0.7819
Pharmacoeconomics
Manufacturers
  • Glaxo group ltd dba glaxosmithkline
Packagers
Dosage forms
FormRouteStrength
OintmentTopical10 mg/g
Prices
Unit descriptionCostUnit
Altabax 1% ointment8.64USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United StatesRE391281998-10-272018-10-27
Canada23075512007-01-012018-10-27
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000394ALOGPS
logP4.63ALOGPS
logP4.37ChemAxon
logS-6.1ALOGPS
pKa (Strongest Acidic)14.43ChemAxon
pKa (Strongest Basic)9.69ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area66.84 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity145.45 m3·mol-1ChemAxon
Polarizability59.49 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Eli Lancry, Lilach Hedvati, Greta Sterimbaum, Ariel Mittelman, Tali Katav, “Amorphous retapamulin and processes for preparation thereof.” U.S. Patent US20090234125, issued September 17, 2009.

US20090234125
General Reference
  1. CenterWatch Link
  2. Jones RN, Fritsche TR, Sader HS, Ross JE: Activity of retapamulin (SB-275833), a novel pleuromutilin, against selected resistant gram-positive cocci. Antimicrob Agents Chemother. 2006 Jul;50(7):2583-6. Pubmed
  3. Yang LP, Keam SJ: Retapamulin: a review of its use in the management of impetigo and other uncomplicated superficial skin infections. Drugs. 2008;68(6):855-73. Pubmed
  4. Novak R, Shlaes DM: The pleuromutilin antibiotics: a new class for human use. Curr Opin Investig Drugs. 2010 Feb;11(2):182-91. Pubmed
  5. Jacobs MR: Retapamulin: a semisynthetic pleuromutilin compound for topical treatment of skin infections in adults and children. Future Microbiol. 2007 Dec;2:591-600. Pubmed
  6. Parish LC, Parish JL: Retapamulin: a new topical antibiotic for the treatment of uncomplicated skin infections. Drugs Today (Barc). 2008 Feb;44(2):91-102. Pubmed
  7. Retapamulin for impetigo and other infections. Drug Ther Bull. 2008 Oct;46(10):76-9. Pubmed
  8. Nagabushan H: Retapamulin: a novel topical antibiotic. Indian J Dermatol Venereol Leprol. 2010 Jan-Feb;76(1):77-9. Pubmed
  9. Shawar R, Scangarella-Oman N, Dalessandro M, Breton J, Twynholm M, Li G, Garges H: Topical retapamulin in the management of infected traumatic skin lesions. Ther Clin Risk Manag. 2009 Feb;5(1):41-9. Epub 2009 Mar 26. Pubmed
External Links
ResourceLink
Therapeutic Targets DatabaseDAP000886
PharmGKBPA164749341
RxListhttp://www.rxlist.com/cgi/generic/altabax.htm
Drugs.comhttp://www.drugs.com/cdi/retapamulin-ointment.html
WikipediaRetapamulin
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. 50S ribosomal protein L3

Kind: protein

Organism: Streptococcus pyogenes serotype M1

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
50S ribosomal protein L3 Q9A1X4 Details

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
  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
  3. Gentry DR, Rittenhouse SF, McCloskey L, Holmes DJ: Stepwise exposure of Staphylococcus aureus to pleuromutilins is associated with stepwise acquisition of mutations in rplC and minimally affects susceptibility to retapamulin. Antimicrob Agents Chemother. 2007 Jun;51(6):2048-52. Epub 2007 Apr 2. Pubmed
  4. Retapamulin for impetigo and other infections. Drug Ther Bull. 2008 Oct;46(10):76-9. Pubmed
  5. Dubois EA, Cohen AF: Retapamulin. Br J Clin Pharmacol. 2010 Jan;69(1):2-3. Pubmed
  6. Nagabushan H: Retapamulin: a novel topical antibiotic. Indian J Dermatol Venereol Leprol. 2010 Jan-Feb;76(1):77-9. Pubmed
  7. Shawar R, Scangarella-Oman N, Dalessandro M, Breton J, Twynholm M, Li G, Garges H: Topical retapamulin in the management of infected traumatic skin lesions. Ther Clin Risk Manag. 2009 Feb;5(1):41-9. Epub 2009 Mar 26. Pubmed
  8. Gelmetti C: Local antibiotics in dermatology. Dermatol Ther. 2008 May-Jun;21(3):187-95. Pubmed
  9. Champney WS, Rodgers WK: Retapamulin inhibition of translation and 50S ribosomal subunit formation in Staphylococcus aureus cells. Antimicrob Agents Chemother. 2007 Sep;51(9):3385-7. Epub 2007 Jun 11. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. GlaxoSmithKline. ALTABAX® (retapamulin) ointment prescribing information. Research Triangle Park, NC; 2010 June.

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Drug created on May 15, 2007 08:24 / Updated on September 16, 2013 17:13