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
  • Retapamulina
External IDs
SB 275833 / SB-275833
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AltabaxOintment10 mg/1gTopicalPhysicians Total Care, Inc.2010-01-072010-03-02Us
AltabaxOintment10 mg/1gTopicalAqua Pharmaceuticals2016-05-01Not applicableUs
AltabaxOintment10 mg/1gTopicalRebel Distributors2010-01-07Not applicableUs
AltabaxOintment10 mg/1gTopicalGlaxosmithkline 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
[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

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.

Associated Conditions
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
DrugInteraction
6-Deoxyerythronolide BThe metabolism of Retapamulin can be decreased when combined with 6-Deoxyerythronolide B.
AcalabrutinibThe metabolism of Retapamulin can be decreased when combined with Acalabrutinib.
AcetaminophenThe metabolism of Retapamulin can be decreased when combined with Acetaminophen.
AcetazolamideThe metabolism of Retapamulin can be decreased when combined with Acetazolamide.
AldesleukinThe metabolism of Retapamulin can be decreased when combined with Aldesleukin.
AlimemazineThe metabolism of Retapamulin can be increased when combined with Alimemazine.
AminoglutethimideThe metabolism of Retapamulin can be increased when combined with Aminoglutethimide.
AmiodaroneThe metabolism of Retapamulin can be decreased when combined with Amiodarone.
AmobarbitalThe metabolism of Retapamulin can be increased when combined with Amobarbital.
Amphotericin BThe metabolism of Retapamulin can be decreased when combined with Amphotericin B.
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
PubChem Compound
6918462
PubChem Substance
46509062
ChemSpider
25064484
ChEMBL
CHEMBL1658
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
  • 84:04.04 — Antibiotics
PDB Entries
2ogo

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentBacterial Infections1
2WithdrawnTreatmentMethicillin-Resistant Staphylococcus Aureus (MRSA) / Orthopedic Procedures1
3CompletedTreatmentSkin Infections, Bacterial1
3RecruitingTreatmentMRSA1
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
  • GlaxoSmithKline Inc.
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
Dosage forms
FormRouteStrength
OintmentTopical10 mg/1g
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)
CA2307551No2007-01-012018-10-27Canada
USRE39128No2006-06-132021-04-12Us
USRE43390No2012-05-152021-04-12Us
US7875630No2011-01-252027-02-14Us
US8207191No2012-06-262024-08-30Us

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 December 10, 2018 13:39