Identification

Name
Retapamulin
Accession Number
DB01256
Type
Small Molecule
Groups
Approved
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
Synonyms
Not Available
External IDs
SB 275833 / SB-275833
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AltabaxOintment10 mg/gTopicalRebel Distributors2010-01-07Not applicableUs
AltabaxOintment10 mg/1TopicalAqua Pharmaceuticals2016-05-01Not applicableUs
AltabaxOintment10 mg/gTopicalPhysicians Total Care, Inc.2010-01-07Not applicableUs
AltabaxOintment10 mg/gTopicalGlaxosmithkline Inc2007-05-022017-01-01Us
AltargoOintment1 %TopicalGlaxosmithkline IncNot applicableNot applicableCanada
Categories
UNII
4MG6O8991R
CAS number
224452-66-8
Weight
Average: 517.763
Monoisotopic: 517.322579687
Chemical Formula
C30H47NO4S
InChI Key
STZYTFJPGGDRJD-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

Pharmacology

Indication

For 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
Pharmacodynamics

Retapamulin 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 action

Retapamulin 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.

TargetActionsOrganism
A50S ribosomal protein L3
inhibitor
Streptococcus pyogenes serotype M1
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

Retapamulin 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 elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Bacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not 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
BoceprevirThe serum concentration of Retapamulin can be increased when it is combined with Boceprevir.Withdrawn
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
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
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
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
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
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.Withdrawn
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 Interactions
Not 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
ChemSpider
25064484
ChEMBL
CHEMBL566434
Therapeutic Targets Database
DAP000886
PharmGKB
PA164749341
HET
G34
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Retapamulin
ATC Codes
D06AX13 — Retapamulin
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentInfections, Bacterial1
2WithdrawnTreatmentMethicillin-Resistant Staphylococcus Aureus (MRSA) / Orthopedic Procedures1
3CompletedTreatmentSkin Infections, Bacterial1
3Not Yet RecruitingTreatmentMRSA1
4Active Not RecruitingPreventionMethicillin-Resistant Staphylococcus Aureus (MRSA)1
4CompletedTreatmentAtopic Dermatitis (AD) / Secondary Infection1
4CompletedTreatmentFolliculitis / Impetigo / Minor Soft Tissue Infections / Secondarily Infected Eczema1
4WithdrawnTreatmentAtopic Dermatitis (AD)1
4WithdrawnTreatmentMethicillin-Resistant Staphylococcus Aureus (MRSA)1
Not AvailableCompletedNot AvailableImpetigo1
Not AvailableCompletedNot AvailableSkin Infections, Bacterial2
Not AvailableCompletedTreatmentFoot Eczema / Hand Eczema1

Pharmacoeconomics

Manufacturers
Not 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
USRE39128 No2001-04-122021-04-12Us
USRE43390 No2001-04-122021-04-12Us
US7875630 No2007-02-142027-02-14Us
US8207191 No2004-08-302024-08-30Us

Properties

State
Solid
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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 )

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as pleuromutilin and derivatives. These are mutilins with a hydroxyacetate derivative attached to the C8 carbon atom of the cyclopenta[8]annulene moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Diterpenoids
Direct Parent
Pleuromutilin and derivatives
Alternative Parents
Tropane alkaloids / Piperidines / N-alkylpyrrolidines / Trialkylamines / Secondary alcohols / Ketones / Carboxylic acid esters / Amino acids and derivatives / Sulfenyl compounds / Monocarboxylic acids and derivatives
show 5 more
Substituents
Pleuromutilin / Tropane alkaloid / Piperidine / N-alkylpyrrolidine / Pyrrolidine / Amino acid or derivatives / Carboxylic acid ester / Ketone / Secondary alcohol / Tertiary amine
show 20 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not 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
Uniprot Name
50S ribosomal protein L3
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da

Drug created on May 15, 2007 08:24 / Updated on October 02, 2017 04:56