Identification

Name
Spiramycin
Accession Number
DB06145
Type
Small Molecule
Groups
Approved
Description

Spiramycin is a macrolide antimicrobial agent with activity against gram-positive organisms, including Streptococcus pyogenes (group A beta-hemolytic streptococci), S. viridans, Corynebacterium diphtheriae, and methicillin-sensitive Staphylococcus aureus. Spiramycin is a 16-membered ring macrolide. It was discovered in 1952 as a product of Streptomyces ambofaciens. As a preparation for oral administration it has been used since 1955, in 1987 also the parenteral form was introduced into practice. The antibacterial spectrum comprises Gram-positive cocci and rods, Gram-negative cocci and also Legionellae, mycoplasmas, chlamydiae, some types of spirochetes, Toxoplasma gondii and Cryptosporidium species. Enterobacteria, pseudomonads and pathogenic moulds are resistant. Its action is mainly bacteriostatic, on highly sensitive strains it exerts a bactericide action.

Structure
Thumb
Synonyms
  • Demycarosylturimycin H
  • foromacidin A
  • Foromacidine A
  • Spiramycin 1
  • Spiramycin A
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Rovamycine 250 Capsule 750000 UnitCapsule750000 unitOralOdan Laboratories Ltd1957-12-31Not applicableCanada
Rovamycine 500 Capsule 1500000 UnitCapsule1500000 unitOralOdan Laboratories Ltd1957-12-31Not applicableCanada
Categories
UNII
033ECH6IFG
CAS number
24916-50-5
Weight
Average: 843.065
Monoisotopic: 842.514005071
Chemical Formula
C43H74N2O14
InChI Key
ACTOXUHEUCPTEW-KWBWCIJSSA-N
InChI
InChI=1S/C43H74N2O14/c1-24-21-29(19-20-46)39(59-42-37(49)36(45(9)10)38(27(4)56-42)58-35-23-43(6,51)41(50)28(5)55-35)40(52-11)31(47)22-33(48)53-25(2)15-13-12-14-16-32(24)57-34-18-17-30(44(7)8)26(3)54-34/h12-14,16,20,24-32,34-42,47,49-51H,15,17-19,21-23H2,1-11H3/b13-12+,16-14+/t24-,25-,26+,27-,28+,29+,30+,31-,32+,34+,35+,36-,37-,38-,39+,40+,41+,42+,43-/m1/s1
IUPAC Name
2-[(4R,5S,6S,7R,9R,10R,11E,13E,16R)-6-{[(2S,3R,4R,5S,6R)-5-{[(2S,4R,5S,6S)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy}-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-10-{[(2R,5S,6S)-5-(dimethylamino)-6-methyloxan-2-yl]oxy}-4-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-1-oxacyclohexadeca-11,13-dien-7-yl]acetaldehyde
SMILES
[H]\C1=C(\[H])/C(/[H])=C([H])/[[email protected]]([H])(O[[email protected]@]2([H])CC[[email protected]]([H])(N(C)C)[[email protected]]([H])(C)O2)[[email protected]]([H])(C)C[[email protected]]([H])(CC=O)[[email protected]]([H])(O[[email protected]]2([H])O[[email protected]]([H])(C)[[email protected]@]([H])(O[[email protected]@]3([H])C[[email protected]@](C)(O)[[email protected]@]([H])(O)[[email protected]]([H])(C)O3)[[email protected]]([H])(N(C)C)[[email protected]@]2([H])O)[[email protected]@]([H])(OC)[[email protected]]([H])(O)CC(=O)O[[email protected]]([H])(C)C1

Pharmacology

Indication

Macrolide antibiotic for treatment of various infections.

Structured Indications
Pharmacodynamics

The absolute bioavailability of oral spiramycin is generally within the range of 30 to 40%. After a 1 g oral dose, the maximum serum drug concentration was found to be within the range 0.4 to 1.4 mg/L.

Mechanism of action

The mechanism of action of macrolides has been a matter of controversy for some time. Spiramycin, a 16-membered macrolide, inhibits translocation by binding to bacterial 50S ribosomal subunits with an apparent 1 : 1 stoichiometry. This antibiotic is a potent inhibitor of the binding to the ribosome of both donor and acceptor substrates. The primary mechanism of action is done by stimulation of dissociation of peptidyl-tRNA from ribosomes during translocation.I

TargetActionsOrganism
A50S ribosomal protein L3
antagonist
inhibitor
Streptococcus pyogenes serotype M1
Absorption

The extent of absorption of Spiramycin was shown to be incomplete. Oral bioavailability ranges from 30-39%. Spiramycin has slower rate of absorption than Erythromycin. It has a high pKa (7.9) which could be a result of high degree of ionization in acidic medium of the stomach.

Volume of distribution

The tissue distribution of spiramycin is extensive. The volume of distribution is in excess of 300 L, and concentrations achieved in bone, muscle, respiratory tract and saliva exceed those found in serum. Spiramycin showed high concentrations in tissues such as: lungs, bronchi, tonsils, and sinuses.

Protein binding

Low level of protein binding (10-25%).

Metabolism

Spiramycin is less metabolised than some of the other macrolides. Metabolism has not been well studied. It is mainly done in the liver to the active metabolites.

Route of elimination

Fecal-biliary route is the primary route of elimination. The secondary route is renal-urinary route.

Half life

Intravenous: Young persons (18 to 32 years of age): Approximately 4.5 to 6.2 hours. Elderly persons (73 to 85 years of age): Approximately 9.8 to 13.5 hours.

Oral: 5.5-8 hours, Rectal in children: 8 hours

Clearance

80% of the administered dose excreted in the bile, which makes the fecal-biliary route is the most important route of elimination. Enterohepatic recycling could also occur. Only 4 to 14% of an administered dose is eliminated through renal-urinary excretion route.

Toxicity

Cardiac toxicity, specifically QT prolongation (irregular heartbeat; recurrent fainting).
Cholestatic hepatitis (abdominal pain; nausea; vomiting; yellow eyes or skin).
Gastrointestinal toxicity, specifically acute colitis (abdominal pain and tenderness; bloody stools; fever).
Intestinal injury (abdominal pain and tenderness). Ulcerated esophagitis (chest pain; heartburn).

Affected organisms
  • Bacteria
  • Bacteria and protozoa
  • Corynebacterium diphtheriae
  • Streptococcus pyogenes
  • Haemophilus influenzae
  • Streptococcus viridans
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be increased when it is combined with Spiramycin.Approved
AcetyldigoxinThe serum concentration of Acetyldigoxin can be increased when it is combined with Spiramycin.Experimental
AmiodaroneThe metabolism of Spiramycin can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Spiramycin can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Spiramycin can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Spiramycin can be decreased when combined with Atomoxetine.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Spiramycin.Investigational
BoceprevirThe metabolism of Spiramycin can be decreased when combined with Boceprevir.Withdrawn
BortezomibThe metabolism of Spiramycin can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Spiramycin can be decreased when it is combined with Bosentan.Approved, Investigational
CarbamazepineThe metabolism of Spiramycin can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Spiramycin can be increased when it is combined with Ceritinib.Approved
CerivastatinThe risk or severity of adverse effects can be increased when Spiramycin is combined with Cerivastatin.Withdrawn
ClarithromycinThe metabolism of Spiramycin can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Spiramycin can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Spiramycin can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Spiramycin can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Spiramycin can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Spiramycin can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Spiramycin can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinThe serum concentration of Cymarin can be increased when it is combined with Spiramycin.Experimental
DabrafenibThe serum concentration of Spiramycin can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Spiramycin can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Spiramycin can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Spiramycin can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Spiramycin can be decreased when combined with Delavirdine.Approved
DeslanosideThe serum concentration of Deslanoside can be increased when it is combined with Spiramycin.Approved
DigitoxinThe serum concentration of Digitoxin can be increased when it is combined with Spiramycin.Approved
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Spiramycin.Approved
DihydroergotamineThe metabolism of Spiramycin can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Spiramycin can be decreased when combined with Diltiazem.Approved
DoxycyclineThe metabolism of Spiramycin can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Spiramycin can be decreased when combined with Dronedarone.Approved
EnzalutamideThe serum concentration of Spiramycin can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Spiramycin can be decreased when combined with Erythromycin.Approved, Vet Approved
FluconazoleThe metabolism of Spiramycin can be decreased when combined with Fluconazole.Approved
FluvastatinThe risk or severity of adverse effects can be increased when Spiramycin is combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Spiramycin can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Spiramycin can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Spiramycin can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Spiramycin can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Spiramycin can be increased when it is combined with Fusidic Acid.Approved
GitoformateThe serum concentration of Gitoformate can be increased when it is combined with Spiramycin.Experimental
IdelalisibThe serum concentration of Spiramycin can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Spiramycin can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Spiramycin can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Spiramycin can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Spiramycin can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Spiramycin can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Spiramycin can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Spiramycin can be decreased when combined with Ketoconazole.Approved, Investigational
Lanatoside CThe serum concentration of Lanatoside C can be increased when it is combined with Spiramycin.Experimental
LopinavirThe metabolism of Spiramycin can be decreased when combined with Lopinavir.Approved
LovastatinThe metabolism of Spiramycin can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Spiramycin can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Spiramycin can be increased when combined with Lumacaftor.Approved
MetildigoxinThe serum concentration of Metildigoxin can be increased when it is combined with Spiramycin.Experimental
MevastatinThe risk or severity of adverse effects can be increased when Spiramycin is combined with Mevastatin.Experimental
MifepristoneThe serum concentration of Spiramycin can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Spiramycin can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Spiramycin can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Spiramycin can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Spiramycin can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Spiramycin can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Spiramycin can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Spiramycin can be decreased when combined with Olaparib.Approved
OleandrinThe serum concentration of Oleandrin can be increased when it is combined with Spiramycin.Experimental
OsimertinibThe serum concentration of Spiramycin can be increased when it is combined with Osimertinib.Approved
OuabainThe serum concentration of Ouabain can be increased when it is combined with Spiramycin.Approved
PalbociclibThe serum concentration of Spiramycin can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe metabolism of Spiramycin can be increased when combined with Pentobarbital.Approved, Vet Approved
PeruvosideThe serum concentration of Peruvoside can be increased when it is combined with Spiramycin.Experimental
PhenobarbitalThe metabolism of Spiramycin can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Spiramycin can be increased when combined with Phenytoin.Approved, Vet Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Spiramycin.Approved
PitavastatinThe risk or severity of adverse effects can be increased when Spiramycin is combined with Pitavastatin.Approved
PosaconazoleThe metabolism of Spiramycin can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe risk or severity of adverse effects can be increased when Spiramycin is combined with Pravastatin.Approved
PrimidoneThe metabolism of Spiramycin can be increased when combined with Primidone.Approved, Vet Approved
ProscillaridinThe serum concentration of Proscillaridin can be increased when it is combined with Spiramycin.Experimental
QuinineThe serum concentration of Quinine can be increased when it is combined with Spiramycin.Approved
RanolazineThe metabolism of Spiramycin can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Spiramycin can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Spiramycin can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Spiramycin can be increased when combined with Rifapentine.Approved
RilpivirineThe serum concentration of Rilpivirine can be increased when it is combined with Spiramycin.Approved
RitonavirThe metabolism of Spiramycin can be decreased when combined with Ritonavir.Approved, Investigational
RosuvastatinThe risk or severity of adverse effects can be increased when Spiramycin is combined with Rosuvastatin.Approved
SaquinavirThe metabolism of Spiramycin can be decreased when combined with Saquinavir.Approved, Investigational
SildenafilThe metabolism of Spiramycin can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Spiramycin can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Spiramycin can be increased when it is combined with Simeprevir.Approved
SimvastatinThe risk or severity of adverse effects can be increased when Spiramycin is combined with Simvastatin.Approved
St. John's WortThe serum concentration of Spiramycin can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Spiramycin can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Spiramycin can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Spiramycin can be decreased when combined with Telaprevir.Withdrawn
TelithromycinThe metabolism of Spiramycin can be decreased when combined with Telithromycin.Approved
TerfenadineSpiramycin may increase the QTc-prolonging activities of Terfenadine.Withdrawn
TiclopidineThe metabolism of Spiramycin can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Spiramycin can be decreased when it is combined with Tocilizumab.Approved
UbidecarenoneThe risk or severity of adverse effects can be increased when Spiramycin is combined with Ubidecarenone.Experimental
VenlafaxineThe metabolism of Spiramycin can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Spiramycin can be decreased when combined with Verapamil.Approved
VinblastineThe serum concentration of Vinblastine can be increased when it is combined with Spiramycin.Approved
VincamineThe serum concentration of Vincamine can be increased when it is combined with Spiramycin.Experimental
VincristineThe serum concentration of Vincristine can be increased when it is combined with Spiramycin.Approved, Investigational
VindesineThe serum concentration of Vindesine can be increased when it is combined with Spiramycin.Approved
VinflunineThe serum concentration of Vinflunine can be increased when it is combined with Spiramycin.Approved
VinorelbineThe serum concentration of Vinorelbine can be increased when it is combined with Spiramycin.Approved, Investigational
VoriconazoleThe metabolism of Spiramycin can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Spiramycin can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

General References
  1. article [Link]
  2. article [Link]
  3. article [Link]
  4. product info [Link]
External Links
ChemSpider
4944970
ChEBI
85260
ChEMBL
CHEMBL1908369
Wikipedia
Spiramycin
ATC Codes
J01FA02 — SpiramycinJ01RA04 — Spiramycin and metronidazole
AHFS Codes
  • 08:12.12 — Macrolides

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentCryptosporidiosis infection / Human Immunodeficiency Virus (HIV) Infections1
4RecruitingTreatmentToxoplasmosis1
Not AvailableCompletedTreatmentCryptosporidiosis infection / Human Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral750000 unit
CapsuleOral1500000 unit
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.196 mg/mLALOGPS
logP2.99ALOGPS
logP2.5ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)12.53ChemAxon
pKa (Strongest Basic)9.28ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count15ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area195.38 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity219.25 m3·mol-1ChemAxon
Polarizability91.68 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

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 aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Aminoglycosides
Alternative Parents
Macrolides and analogues / Disaccharides / O-glycosyl compounds / Oxanes / Alpha-hydrogen aldehydes / Tertiary alcohols / 1,2-aminoalcohols / Trialkylamines / Amino acids and derivatives / Carboxylic acid esters
show 9 more
Substituents
Aminoglycoside core / Macrolide / Disaccharide / Glycosyl compound / O-glycosyl compound / Oxane / Alpha-hydrogen aldehyde / Tertiary alcohol / 1,2-aminoalcohol / Amino acid or derivatives
show 22 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
tertiary amino compound, disaccharide derivative, ether, macrolide, aldehyde (CHEBI:85260)

Targets

Kind
Protein
Organism
Streptococcus pyogenes serotype M1
Pharmacological action
Yes
Actions
Antagonist
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

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
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on November 19, 2007 09:52 / Updated on October 21, 2017 09:34