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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
External Identifiers
  • SB 275833
  • SB-275833
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Altabaxointment10 mg/gtopicalGlaxo Smith Kline Llc2007-05-02Not applicableUs
Altabaxointment10 mg/gtopicalPhysicians Total Care, Inc.2010-01-07Not applicableUs
Altabaxointment10 mg/gtopicalRebel Distributors Corp.2010-01-07Not applicableUs
Altargoointment1 %topicalGlaxosmithkline IncNot applicableNot applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII4MG6O8991R
CAS number224452-66-8
WeightAverage: 517.763
Monoisotopic: 517.322579687
Chemical FormulaC30H47NO4S
InChI KeySTZYTFJPGGDRJD-NHUWBDDWSA-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[5.4.3.0¹,⁸]tetradecan-6-yl 2-{[(1R,3S,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl]sulfanyl}acetate
SMILES
[H][C@]12CC[C@]([H])(C[C@]([H])(C1)SCC(=O)O[C@]1([H])C[C@@](C)(C=C)[C@@]([H])(O)[C@]([H])(C)[C@]34CCC(=O)[C@@]3([H])[C@@]1(C)[C@]([H])(C)CC4)N2C
Taxonomy
ClassificationNot classified
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+0.5359
Blood Brain Barrier+0.8647
Caco-2 permeable+0.5282
P-glycoprotein substrateSubstrate0.6692
P-glycoprotein inhibitor IInhibitor0.881
P-glycoprotein inhibitor IIInhibitor0.7432
Renal organic cation transporterInhibitor0.5618
CYP450 2C9 substrateNon-substrate0.7457
CYP450 2D6 substrateNon-substrate0.7732
CYP450 3A4 substrateSubstrate0.7848
CYP450 1A2 substrateNon-inhibitor0.7993
CYP450 2C9 inhibitorNon-inhibitor0.7935
CYP450 2D6 inhibitorNon-inhibitor0.882
CYP450 2C19 inhibitorNon-inhibitor0.8004
CYP450 3A4 inhibitorNon-inhibitor0.5938
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8717
Ames testNon AMES toxic0.7256
CarcinogenicityNon-carcinogens0.9557
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7920 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9704
hERG inhibition (predictor II)Non-inhibitor0.7819
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Ointmenttopical10 mg/g
Ointmenttopical1 %
Prices
Unit descriptionCostUnit
Altabax 1% ointment8.64USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2307551 No2007-01-012018-10-27Canada
US7875630 No2007-02-142027-02-14Us
USRE39128 No2001-04-122021-04-12Us
USRE43390 No2001-04-122021-04-12Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000394 mg/mLALOGPS
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
Polarizability57.94 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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 References
  1. 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:16801451 ]
  2. 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:18416589 ]
  3. Novak R, Shlaes DM: The pleuromutilin antibiotics: a new class for human use. Curr Opin Investig Drugs. 2010 Feb;11(2):182-91. [PubMed:20112168 ]
  4. Jacobs MR: Retapamulin: a semisynthetic pleuromutilin compound for topical treatment of skin infections in adults and children. Future Microbiol. 2007 Dec;2(6):591-600. [PubMed:18041900 ]
  5. 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. doi: 10.1358/dot.2008.44.2.1153446. [PubMed:18389088 ]
  6. Authors unspecified: Retapamulin for impetigo and other infections. Drug Ther Bull. 2008 Oct;46(10):76-9. doi: 10.1136/dtb.2008.09.0023. [PubMed:18832258 ]
  7. Nagabushan H: Retapamulin: a novel topical antibiotic. Indian J Dermatol Venereol Leprol. 2010 Jan-Feb;76(1):77-9. doi: 10.4103/0378-6323.58693. [PubMed:20061745 ]
  8. 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:19436611 ]
  9. Link [Link]
External Links
ATC CodesD06AX13
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AtazanavirThe serum concentration of Retapamulin can be increased when it is combined with Atazanavir.
BoceprevirThe serum concentration of Retapamulin can be increased when it is combined with Boceprevir.
CeritinibThe serum concentration of Retapamulin can be increased when it is combined with Ceritinib.
ClarithromycinThe serum concentration of Retapamulin can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Retapamulin can be increased when it is combined with Cobicistat.
DarunavirThe serum concentration of Retapamulin can be increased when it is combined with Darunavir.
IdelalisibThe serum concentration of Retapamulin can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Retapamulin can be increased when it is combined with Indinavir.
ItraconazoleThe serum concentration of Retapamulin can be increased when it is combined with Itraconazole.
KetoconazoleThe serum concentration of Retapamulin can be increased when it is combined with Ketoconazole.
NefazodoneThe serum concentration of Retapamulin can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Retapamulin can be increased when it is combined with Nelfinavir.
PosaconazoleThe serum concentration of Retapamulin can be increased when it is combined with Posaconazole.
RitonavirThe serum concentration of Retapamulin can be increased when it is combined with Ritonavir.
SaquinavirThe serum concentration of Retapamulin can be increased when it is combined with Saquinavir.
TelaprevirThe serum concentration of Retapamulin can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Retapamulin can be increased when it is combined with Telithromycin.
VoriconazoleThe serum concentration of Retapamulin can be increased when it is combined with Voriconazole.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Streptococcus pyogenes serotype M1
Pharmacological action
yes
Actions
inhibitor
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
rplC
Uniprot ID:
Q9A1X4
Molecular Weight:
22438.035 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 ]
  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:17404009 ]
  4. Authors unspecified: Retapamulin for impetigo and other infections. Drug Ther Bull. 2008 Oct;46(10):76-9. doi: 10.1136/dtb.2008.09.0023. [PubMed:18832258 ]
  5. Dubois EA, Cohen AF: Retapamulin. Br J Clin Pharmacol. 2010 Jan;69(1):2-3. doi: 10.1111/j.1365-2125.2009.03505.x. [PubMed:20078606 ]
  6. Nagabushan H: Retapamulin: a novel topical antibiotic. Indian J Dermatol Venereol Leprol. 2010 Jan-Feb;76(1):77-9. doi: 10.4103/0378-6323.58693. [PubMed:20061745 ]
  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:19436611 ]
  8. Gelmetti C: Local antibiotics in dermatology. Dermatol Ther. 2008 May-Jun;21(3):187-95. doi: 10.1111/j.1529-8019.2008.00190.x. [PubMed:18564249 ]
  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:17562806 ]

Enzymes

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Comments
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Drug created on May 15, 2007 08:24 / Updated on June 30, 2016 01:50