Identification

Name
Midecamycin
Accession Number
DB13456
Type
Small Molecule
Groups
Approved
Description

Midecamycin is a naturally occurring 16-membered macrolide[1] that fits under the category of acetoxy-substituted macrolide antibiotics. In this molecule, an acetoxy group is substituted on the position 9 of the 16-member ring and on position 4 of the terminal sugar.[2] Until 2017, midecamycin was still under the list of approved antimicrobial active pharmaceutical ingredients by Health Canada.[9]

Structure
Thumb
Synonyms
  • Espinomycin A
  • Medecamycin A1
  • Medemycin A1
  • Midecamycin A1
  • Momicine
  • Mydecamycin A1
  • Platenomycin B1
  • Rubimycin
  • Turimycin P3
External IDs
NSC-154011 / SF-837 / SF-837A1 / YL-704B1
International/Other Brands
Medemycin (Main Life Corporation)
Categories
UNII
N34Z0Y5UH7
CAS number
35457-80-8
Weight
Average: 813.979
Monoisotopic: 813.451070461
Chemical Formula
C41H67NO15
InChI Key
DMUAPQTXSSNEDD-QALJCMCCSA-N
InChI
InChI=1S/C41H67NO15/c1-11-30(45)54-29-21-32(47)51-24(4)16-14-13-15-17-28(44)23(3)20-27(18-19-43)37(38(29)50-10)57-40-35(48)34(42(8)9)36(25(5)53-40)56-33-22-41(7,49)39(26(6)52-33)55-31(46)12-2/h13-15,17,19,23-29,33-40,44,48-49H,11-12,16,18,20-22H2,1-10H3/b14-13+,17-15+/t23-,24-,25-,26+,27+,28+,29-,33+,34-,35-,36-,37+,38+,39+,40+,41-/m1/s1
IUPAC Name
(2S,3S,4R,6S)-6-{[(2R,3S,4R,5R,6S)-4-(dimethylamino)-5-hydroxy-6-{[(4R,5S,6S,7R,9R,10R,11E,13E,16R)-10-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-7-(2-oxoethyl)-4-(propanoyloxy)-1-oxacyclohexadeca-11,13-dien-6-yl]oxy}-2-methyloxan-3-yl]oxy}-4-hydroxy-2,4-dimethyloxan-3-yl propanoate
SMILES
[H][C@@]1(C[C@@](C)(O)[C@@H](OC(=O)CC)[C@H](C)O1)O[C@@H]1[C@@H](C)O[C@@]([H])(O[C@H]2[C@@H](CC=O)C[C@@H](C)[C@@H](O)\C=C\C=C\C[C@@H](C)OC(=O)C[C@@]([H])(OC(=O)CC)[C@@H]2OC)[C@H](O)[C@H]1N(C)C

Pharmacology

Indication

Midecamycin was used for the treatment of infections in the oral cavity, upper and lower respiratory tracts and skin and soft tissue infections. The alone use of midecamycin was mainly used in Europe or Japan.[7]

Pharmacodynamics

Reports have indicated that midecamycin is active against both erythromycin-susceptible and efflux-mediated erythromycin-resistant strains. The diacetate form of this product reduces gastrointestinal side effects and improves its pharmacokinetic profile.[1] Studies have proved that midecamycin is highly active against Gram-positive organisms.[6] The activity of midecamycin in the form of acetate salt presents a better activity, which seems to be potentiated at pH 7-8, as well as a longer half-life.[5]

Mechanism of action

Midecamycin, as part of the macrolides, act by inhibiting bacterial protein synthesis. More specifically, midecamycin inhibits bacterial growth by targetting the 50S ribosomal subunit preventing peptide bond formation and translocation during protein synthesis. The presence of mutations in the 50S RNA can prevent midecamycin binding. Midecamycin is a broad spectrum antibiotic and thus, it can interact with different bacteria.[8]

Absorption

Midecamycin is rapidly and almost completely absorbed when orally administered.[2] It is mainly absorbed in the alkaline intestinal environment. This rapid absorption is due to its liposoluble property which allows for good penetration in the tissues, especially bronchial secretion, prostatic tissue, middle ear exudates and bone tissue. The tissue/serum ratio concentration is greater than 1 which indicates that this product does not stay long in the plasma. After oral administration of 600 mg of midecamycin, the peak serum concentration is 0.8 mg/L and it is attained 1 hour after oral administration. This concentration dereased significantly after 4-6 hours.[3]

Volume of distribution

The reported apparent volume of distribution of midecamycin is 7.7 L/kg.[4]

Protein binding

Midecamycin does not bind to plasma proteins in a significant proportion and thus, the bound form can account for about 15% of the administered dose.[3] The acetate form of midecamycin presents a larger protein binding.[5]

Metabolism

Midecamycin undergoes extensive biotransformation in the liver and its metabolites are characterized by presenting little to no antimicrobial activity. The main metabolite is formed by a 14-hydroxylation and it can be also detected in urine.[3]

Route of elimination

The major route of elimination of midecamycin is is the liver, followed by a low significance of renal elimination. Urinary concentrations accounts for about 3.3% of the administered dose after 6 hours.[3]

Half life

The half-life of midecamycin is longer than the first macrolide antibiotics.[3] after intravenous administration, the half-life reported is of 54 minutes.[4]

Clearance

Midecamycin presentas a low renal clearance value.[3]

Toxicity
Not Available
Affected organisms
  • Gram-positive Bacteria
  • Corynebacterium diphtheriae
  • Bordetella pertussis
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
Acetyl sulfisoxazoleThe metabolism of Midecamycin can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet Approved
AmiodaroneThe metabolism of Midecamycin can be decreased when combined with Amiodarone.Approved, Investigational
ApalutamideThe serum concentration of Midecamycin can be decreased when it is combined with Apalutamide.Approved, Investigational
AprepitantThe serum concentration of Midecamycin can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Midecamycin can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Midecamycin can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe risk or severity of rhabdomyolysis can be increased when Midecamycin is combined with Atorvastatin.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Midecamycin.Investigational
BoceprevirThe metabolism of Midecamycin can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Midecamycin can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Midecamycin can be decreased when it is combined with Bosentan.Approved, Investigational
CaffeineThe metabolism of Caffeine can be decreased when combined with Midecamycin.Approved
CarbamazepineThe metabolism of Carbamazepine can be decreased when combined with Midecamycin.Approved, Investigational
CeritinibThe serum concentration of Midecamycin can be increased when it is combined with Ceritinib.Approved
CerivastatinThe risk or severity of rhabdomyolysis can be increased when Midecamycin is combined with Cerivastatin.Approved, Withdrawn
ClarithromycinThe metabolism of Midecamycin can be decreased when combined with Clarithromycin.Approved
ClotrimazoleThe metabolism of Midecamycin can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Midecamycin can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Midecamycin.Approved, Investigational
CrizotinibThe metabolism of Midecamycin can be decreased when combined with Crizotinib.Approved
CurcuminThe metabolism of Midecamycin can be decreased when combined with Curcumin.Approved, Investigational
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Midecamycin.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Midecamycin can be decreased when it is combined with Dabrafenib.Approved, Investigational
DarunavirThe metabolism of Midecamycin can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Midecamycin can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Midecamycin can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Midecamycin can be decreased when combined with Delavirdine.Approved
DexamethasoneThe serum concentration of Midecamycin can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DihydroergotamineThe metabolism of Midecamycin can be decreased when combined with Dihydroergotamine.Approved, Investigational
DiltiazemThe metabolism of Midecamycin can be decreased when combined with Diltiazem.Approved, Investigational
DoxycyclineThe metabolism of Midecamycin can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Midecamycin can be decreased when combined with Dronedarone.Approved
EnzalutamideThe serum concentration of Midecamycin can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Midecamycin can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
FluconazoleThe metabolism of Midecamycin can be decreased when combined with Fluconazole.Approved, Investigational
FluvoxamineThe metabolism of Midecamycin can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Midecamycin can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Midecamycin can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Midecamycin can be increased when combined with Fosphenytoin.Approved, Investigational
Fusidic AcidThe serum concentration of Midecamycin can be increased when it is combined with Fusidic Acid.Approved, Investigational
GanciclovirThe metabolism of Ganciclovir can be decreased when combined with Midecamycin.Approved, Investigational
HydrocodoneThe metabolism of Hydrocodone can be decreased when combined with Midecamycin.Approved, Illicit
IdelalisibThe metabolism of Midecamycin can be decreased when combined with Idelalisib.Approved
ImatinibThe metabolism of Midecamycin can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Midecamycin can be decreased when combined with Indinavir.Approved
IsavuconazoleThe serum concentration of Midecamycin can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of Midecamycin can be decreased when combined with Isavuconazonium.Approved, Investigational
ItraconazoleThe metabolism of Midecamycin can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Midecamycin can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Midecamycin can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of Midecamycin can be decreased when combined with Lopinavir.Approved
LorpiprazoleThe serum concentration of Midecamycin can be increased when it is combined with Lorpiprazole.Approved
LovastatinThe risk or severity of rhabdomyolysis can be increased when Midecamycin is combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Midecamycin can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Midecamycin can be increased when combined with Lumacaftor.Approved
MevastatinThe risk or severity of rhabdomyolysis can be increased when Midecamycin is combined with Mevastatin.Experimental
MibefradilThe metabolism of Midecamycin can be decreased when combined with Mibefradil.Investigational, Withdrawn
MiconazoleThe metabolism of Midecamycin can be decreased when combined with Miconazole.Approved, Investigational, Vet Approved
MifepristoneThe serum concentration of Midecamycin can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Midecamycin can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Midecamycin can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Midecamycin can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Midecamycin can be increased when it is combined with Netupitant.Approved, Investigational
NevirapineThe metabolism of Midecamycin can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Midecamycin can be decreased when combined with Nicardipine.Approved, Investigational
NilotinibThe metabolism of Midecamycin can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Midecamycin can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Midecamycin can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Midecamycin can be increased when it is combined with Palbociclib.Approved, Investigational
PentobarbitalThe metabolism of Midecamycin can be increased when combined with Pentobarbital.Approved, Investigational, Vet Approved
PhenobarbitalThe metabolism of Midecamycin can be increased when combined with Phenobarbital.Approved, Investigational
PhenytoinThe metabolism of Midecamycin 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 Midecamycin.Approved
PitavastatinThe risk or severity of rhabdomyolysis can be increased when Midecamycin is combined with Pitavastatin.Approved
PitolisantThe serum concentration of Midecamycin can be decreased when it is combined with Pitolisant.Approved, Investigational
PosaconazoleThe metabolism of Midecamycin can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe risk or severity of rhabdomyolysis can be increased when Midecamycin is combined with Pravastatin.Approved
PrimidoneThe metabolism of Midecamycin can be increased when combined with Primidone.Approved, Vet Approved
RanolazineThe metabolism of Midecamycin can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Midecamycin can be increased when combined with Rifabutin.Approved, Investigational
RifampicinThe metabolism of Midecamycin can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Midecamycin can be increased when combined with Rifapentine.Approved, Investigational
RucaparibThe metabolism of Midecamycin can be decreased when combined with Rucaparib.Approved, Investigational
SaquinavirThe metabolism of Midecamycin can be decreased when combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Midecamycin can be decreased when used in combination with Sarilumab.Approved, Investigational
SildenafilThe metabolism of Midecamycin can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Midecamycin can be decreased when it is combined with Siltuximab.Approved, Investigational
SimeprevirThe serum concentration of Midecamycin can be increased when it is combined with Simeprevir.Approved
SimvastatinThe risk or severity of rhabdomyolysis can be increased when Midecamycin is combined with Simvastatin.Approved
St. John's WortThe serum concentration of Midecamycin can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
StiripentolThe serum concentration of Midecamycin can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Midecamycin can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Midecamycin can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Midecamycin can be decreased when combined with Telithromycin.Approved
TiclopidineThe metabolism of Midecamycin can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Midecamycin can be decreased when it is combined with Tocilizumab.Approved
ValaciclovirThe metabolism of Valaciclovir can be decreased when combined with Midecamycin.Approved, Investigational
VemurafenibThe serum concentration of Midecamycin can be decreased when it is combined with Vemurafenib.Approved
VerapamilThe metabolism of Midecamycin can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Midecamycin can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Midecamycin can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

General References
  1. Schlegel L, Merad B, Rostane H, Broc V, Bouvet A: In vitro activity of midecamycin diacetate, a 16-membered macrolide, against Streptococcus pyogenes isolated in France, 1995-1999. Clin Microbiol Infect. 2001 Jul;7(7):362-6. [PubMed:11531981]
  2. Neu HC: In vitro activity of midecamycin, a new macrolide antibiotic. Antimicrob Agents Chemother. 1983 Sep;24(3):443-4. [PubMed:6639001]
  3. Periti P, Mazzei T, Mini E, Novelli A: Clinical pharmacokinetic properties of the macrolide antibiotics. Effects of age and various pathophysiological states (Part I). Clin Pharmacokinet. 1989 Apr;16(4):193-214. doi: 10.2165/00003088-198916040-00001. [PubMed:2656049]
  4. Inoue A, Deguchi T: [The pharmacokinetic studies on spiramycin and acetylspiramycin in rats]. Jpn J Antibiot. 1982 Aug;35(8):1998-2004. [PubMed:7154248]
  5. Yoshida T, Watanabe T, Shomura T, Someya S, Okamoto R, Ishihara S, Miyauchi K, Kazuno Y: Bacteriological evaluation of midecamycin acetate and its metabolites. Jpn J Antibiot. 1982 Jun;35(6):1462-74. [PubMed:6982352]
  6. Bycroft B. and Payne D. (2014). Dictionary of Antibiotic and Related Substances (2nd ed.). CRC Press.
  7. Omura S. (2002). Macrolide antibiotics: Chemistry, Biology and Practice (2nd ed.). Academic Press.
  8. Garbis H., Tonningen M. and Reuvers M. (2007). Drugs during Pregnancy and Lactation (2nd ed.). Academic Press.
  9. Health Canada Approved ingredients list [Link]
External Links
KEGG Drug
D01339
ChemSpider
4445365
ChEBI
31845
ChEMBL
CHEMBL444963
Wikipedia
Midecamycin
ATC Codes
J01FA03 — Midecamycin
MSDS
Download (52.4 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)155 ºC'MSDS'
boiling point (°C)874 ºC'MSDS'
water solubilityInsoluble'MSDS'
logP2.22 Bycroft B. and Payne D. Dictionary of antibiotics. (2014)
pKa6.9Omura S. Macrolide Antibiotics. (2002)
Predicted Properties
PropertyValueSource
Water Solubility0.0935 mg/mLALOGPS
logP3.09ALOGPS
logP3.19ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)12.71ChemAxon
pKa (Strongest Basic)7.9ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area206.05 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity206.51 m3·mol-1ChemAxon
Polarizability85.96 Å3ChemAxon
Number of Rings3ChemAxon
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 / Tricarboxylic acids and derivatives / Oxanes / Alpha-hydrogen aldehydes / Tertiary alcohols / 1,2-aminoalcohols / Trialkylamines / Amino acids and derivatives
show 9 more
Substituents
Aminoglycoside core / Macrolide / Disaccharide / Glycosyl compound / O-glycosyl compound / Tricarboxylic acid or derivatives / Oxane / Alpha-hydrogen aldehyde / Tertiary alcohol / 1,2-aminoalcohol
show 22 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not Available

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
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. von Rosensteil NA, Adam D: Macrolide antibacterials. Drug interactions of clinical significance. Drug Saf. 1995 Aug;13(2):105-22. [PubMed:7576262]
  2. Kuper JI, D'Aprile M: Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. Clin Pharmacokinet. 2000 Sep;39(3):203-14. [PubMed:11020135]

Drug created on June 23, 2017 14:42 / Updated on August 02, 2018 06:52