Identification

Name
Midecamycin
Accession Number
DB13456
Type
Small Molecule
Groups
Experimental
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
DrugInteraction
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Midecamycin.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Midecamycin.
3-isobutyl-1-methyl-7H-xanthineThe metabolism of 3-isobutyl-1-methyl-7H-xanthine can be decreased when combined with Midecamycin.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Midecamycin.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Midecamycin.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Midecamycin.
6-Deoxyerythronolide BThe metabolism of Midecamycin can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Midecamycin.
7-DeazaguanineThe metabolism of 7-Deazaguanine can be decreased when combined with Midecamycin.
7,9-DimethylguanineThe metabolism of 7,9-Dimethylguanine can be decreased when combined with Midecamycin.
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 November 02, 2018 07:40