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])/[C@]([H])(O[C@@]2([H])CC[C@]([H])(N(C)C)[C@]([H])(C)O2)[C@]([H])(C)C[C@]([H])(CC=O)[C@]([H])(O[C@]2([H])O[C@]([H])(C)[C@@]([H])(O[C@@]3([H])C[C@@](C)(O)[C@@]([H])(O)[C@]([H])(C)O3)[C@]([H])(N(C)C)[C@@]2([H])O)[C@@]([H])(OC)[C@]([H])(O)CC(=O)O[C@]([H])(C)C1

Pharmacology

Indication

Macrolide antibiotic for treatment of various infections.

Associated Conditions
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
DrugInteraction
AcetazolamideThe metabolism of Spiramycin can be decreased when combined with Acetazolamide.
AlbendazoleThe metabolism of Albendazole can be decreased when combined with Spiramycin.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Spiramycin.
AlfentanilThe metabolism of Alfentanil can be decreased when combined with Spiramycin.
AlfuzosinThe metabolism of Alfuzosin can be decreased when combined with Spiramycin.
AlmotriptanThe metabolism of Almotriptan can be decreased when combined with Spiramycin.
AlosetronThe metabolism of Alosetron can be decreased when combined with Spiramycin.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Spiramycin.
AmcinonideThe metabolism of Amcinonide can be decreased when combined with Spiramycin.
AmiodaroneThe metabolism of Spiramycin can be decreased when combined with Amiodarone.
Food Interactions
Not Available

References

General References
  1. article [Link]
  2. article [Link]
  3. article [Link]
  4. product info [Link]
External Links
PubChem Compound
6440717
PubChem Substance
347827756
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
Inhibitor
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]
  2. Spina E, Pisani F, Perucca E: Clinically significant pharmacokinetic drug interactions with carbamazepine. An update. Clin Pharmacokinet. 1996 Sep;31(3):198-214. doi: 10.2165/00003088-199631030-00004. [PubMed:8877250]

Drug created on November 19, 2007 09:52 / Updated on October 16, 2018 08:38