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Identification
NameRetapamulin
Accession NumberDB01256
TypeSmall Molecule
GroupsApproved
DescriptionRetapamulin 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/1TopicalAqua Pharmaceuticals2016-05-01Not applicableUs
AltabaxOintment10 mg/gTopicalRebel Distributors Corp.2010-01-07Not applicableUs
AltabaxOintment10 mg/gTopicalPhysicians Total Care, Inc.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
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.
Structured Indications
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.
TargetKindPharmacological actionActionsOrganismUniProt ID
50S ribosomal protein L3Proteinyes
inhibitor
Streptococcus pyogenes serotype M1Q9A1X4 details
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
Interactions
Drug Interactions
DrugInteractionDrug group
AmiodaroneThe serum concentration of Retapamulin can be increased when it is combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Retapamulin can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe serum concentration of Retapamulin can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Retapamulin can be decreased when combined with Atomoxetine.Approved
BexaroteneThe serum concentration of Retapamulin can be decreased when it is combined with Bexarotene.Approved, Investigational
BoceprevirThe serum concentration of Retapamulin can be increased when it is combined with Boceprevir.Approved
BortezomibThe metabolism of Retapamulin can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Retapamulin can be decreased when it is combined with Bosentan.Approved, Investigational
CarbamazepineThe metabolism of Retapamulin can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Retapamulin can be increased when it is combined with Ceritinib.Approved
ClarithromycinThe serum concentration of Retapamulin can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Retapamulin can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Retapamulin can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Retapamulin can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Retapamulin can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Retapamulin can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Retapamulin can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Retapamulin can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe serum concentration of Retapamulin can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Retapamulin can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Retapamulin can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Retapamulin can be decreased when combined with Delavirdine.Approved
DexamethasoneThe serum concentration of Retapamulin can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DihydroergotamineThe metabolism of Retapamulin can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Retapamulin can be decreased when combined with Diltiazem.Approved
DoxycyclineThe metabolism of Retapamulin can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Retapamulin can be decreased when combined with Dronedarone.Approved
EfavirenzThe serum concentration of Retapamulin can be decreased when it is combined with Efavirenz.Approved, Investigational
EnzalutamideThe serum concentration of Retapamulin can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Retapamulin can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Retapamulin can be decreased when it is combined with Eslicarbazepine acetate.Approved
EtravirineThe serum concentration of Retapamulin can be decreased when it is combined with Etravirine.Approved
FluconazoleThe metabolism of Retapamulin can be decreased when combined with Fluconazole.Approved
FluvoxamineThe metabolism of Retapamulin can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Retapamulin can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Retapamulin can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Retapamulin can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Retapamulin can be increased when it is combined with Fusidic Acid.Approved
IdelalisibThe serum concentration of Retapamulin can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Retapamulin can be decreased when combined with Imatinib.Approved
IndinavirThe serum concentration of Retapamulin can be increased when it is combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Retapamulin can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Retapamulin can be decreased when combined with Isradipine.Approved
ItraconazoleThe serum concentration of Retapamulin can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Retapamulin can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe serum concentration of Retapamulin can be increased when it is combined with Ketoconazole.Approved, Investigational
LopinavirThe serum concentration of Retapamulin can be increased when it is combined with Lopinavir.Approved
LovastatinThe metabolism of Retapamulin can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Retapamulin can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Retapamulin can be increased when combined with Lumacaftor.Approved
MifepristoneThe serum concentration of Retapamulin can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Retapamulin can be decreased when it is combined with Mitotane.Approved
ModafinilThe serum concentration of Retapamulin can be decreased when it is combined with Modafinil.Approved, Investigational
NafcillinThe serum concentration of Retapamulin can be decreased when it is combined with Nafcillin.Approved
NefazodoneThe serum concentration of Retapamulin can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Retapamulin can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Retapamulin can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Retapamulin can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Retapamulin can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Retapamulin can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Retapamulin can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Retapamulin can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe metabolism of Retapamulin can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Retapamulin can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Retapamulin can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe serum concentration of Retapamulin can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Retapamulin can be increased when combined with Primidone.Approved, Vet Approved
RanolazineThe metabolism of Retapamulin can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Retapamulin can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Retapamulin can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Retapamulin can be increased when combined with Rifapentine.Approved
RitonavirThe serum concentration of Retapamulin can be increased when it is combined with Ritonavir.Approved, Investigational
SaquinavirThe serum concentration of Retapamulin can be increased when it is combined with Saquinavir.Approved, Investigational
SildenafilThe metabolism of Retapamulin can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Retapamulin can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Retapamulin can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Retapamulin can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Retapamulin can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Retapamulin can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe serum concentration of Retapamulin can be increased when it is combined with Telaprevir.Approved
TelithromycinThe serum concentration of Retapamulin can be increased when it is combined with Telithromycin.Approved
TiclopidineThe metabolism of Retapamulin can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Retapamulin can be decreased when it is combined with Tocilizumab.Approved
VenlafaxineThe metabolism of Retapamulin can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Retapamulin can be decreased when combined with Verapamil.Approved
VoriconazoleThe serum concentration of Retapamulin can be increased when it is combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Retapamulin can be decreased when combined with Ziprasidone.Approved
Food InteractionsNot 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
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
OintmentTopical10 mg/1
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
Taxonomy
ClassificationNot classified

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 December 09, 2016 02:38