Mitomycin C

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Structural formula
Structural formula of mitomycin
General
Non-proprietary name Mitomycin
other names

[(1a S , 8 S , 8a R , 8b S ) -6-amino-8a-methoxy-5-methyl-4,7-dioxo-1,1a, 2,4,7,8,8a, 8b-octahydroazirino [2.3: 3.4] pyrrolo [1,2- a ] indol-8-ylmethyl] carbamate

Molecular formula C 15 H 18 N 4 O 5
Brief description

blue-purple odorless powder

External identifiers / databases
CAS number 50-07-7
EC number 200-008-6
ECHA InfoCard 100,000,008
PubChem 5746
ChemSpider 5544
DrugBank DB00305
Wikidata Q19856779
Drug information
ATC code

L01 DC03

Drug class

Cytostatics

properties
Molar mass 334.33 g · mol -1
Melting point

> 360 ° C

pK s value

10.9

solubility

8.4 mg / ml in water; also soluble in acetone and methanol

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
06 - Toxic or very toxic 08 - Dangerous to health

danger

H and P phrases H: 300-351
P: 270-280-301 + 310-405
Toxicological data

30 mg kg −1 ( LD 50 ,  rat ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Mitomycin C , often referred to simply as mitomycin , is a drug from the group of mitomycins and is used as a cytostatic . It belongs to the so-called tumor antibiotics .

introduction

Mitomycin C is an antibiotic and was isolated from Streptomyces caespitosus in 1958 . It is effective against gram- positive bacteria and some viruses . Today it is only used as a cytostatic agent.

pharmacology

Mechanism of action

After enzymatic activation, it inhibits DNA synthesis. Mitomycin C intercalates between two strands of DNA. As a result, the DNA strands are covalently connected to one another, so that a dissociation of the DNA strands, as is required for replication or also for transcription , is no longer possible. As a result of the DNA damage, which is often irreparable for the cell, activation of certain signal cascades triggers an arrest of the cell cycle with subsequent apoptosis .

Absorption and distribution in the body (pharmacokinetics)

After intravenous administration, high concentrations of mitomycin C are found in the kidneys , muscles , heart , lungs , tongue , bile and urine . The substance is quickly inactivated by enzymes in the liver, kidney, spleen and heart . It is mainly excreted via the kidneys.

Adverse effects (side effects)

frequent side effects

side effect index
Bone marrow damage 1
Skin necrosis 3
skin rash 1
Hair loss 0
Inflammation of the mucous membranes 0
Nausea + vomiting 1
Liver damage 0
Damage to the heart 1
allergy 0
Lung fibrosis 2
Kidney damage 2
CNS damage 0
Peripheral neuropathy 0

0 = very gentle or very seldom; 1 = occasional but not severe; 2 = significant; 3 = severe or frequent

Drug interactions

  • The combination with vinca alkaloids and bleomycin increases the lung damaging effect.
  • The simultaneous administration of doxorubicin and mitomycin C increases the cardiac damaging effect of doxorubicin.
  • Vitamin B 6 administration leads to a loss of effectiveness of mitomycin C.

Application areas (indications)

It is also used after certain surgical procedures on the eye to prevent scarring ( prescription drugs , phosphate-buffered eye drops).

Contraindications (contraindications)

  • Decreased bone marrow function
  • Bleeding tendency
  • Liver, lung and kidney damage
  • poor general condition
  • known hypersensitivity to mitomycin C.

Analytics

Methods for the reliable quantification of mitomycin C in different matrices are available for therapy control and for minimizing undesirable drug effects. After adequate sample preparation , combinations of chromatographic separation methods with mass spectrometry are used .

Trade names

Monopreparations

Amétycine (D), Mitem (D), Urocin (D), Mito-medac (D), various generics (D, A)

Individual evidence

  1. ↑ a b Mitomycin C data sheet (PDF) from Carl Roth , accessed on February 24, 2013.
  2. ↑ a b Entry on Mitomycins. In: Römpp Online . Georg Thieme Verlag, accessed on July 1, 2019.
  3. ↑ a b c Entry on Mitomycin C in the GESTIS substance database of the IFA , accessed on January 23, 2020(JavaScript required) .
  4. ↑ Mitomycins - Lexicon of Biology. In: Spektrum.de. March 27, 2014, accessed May 4, 2015 .
  5. ↑ Eberhard Aulbert, Wiebke Nehls: Palliative internal-oncological tumor therapy. In: Eberhard Aulbert, Friedemann Nauck, Lukas Radbruch (eds.): Textbook of palliative medicine. Schattauer, Stuttgart (1997) 3rd, updated edition 2012, ISBN 978-3-7945-2666-6 , pp. 633-663, here: p. 644.
  6. ↑ pharmische-zeitung.de: Surgical treatment of eye diseases (accessed on January 3, 2017)
  7. ^ DAC / NRF , 2012.
  8. ^ Y. Tang, S. Zhang, X. Li, X. Sun, N. Wen, M. Yu, L. Peng, J. Li, Z. Li, B. Li: Determination of mitomycin C in rabbit plasma by ultra -high performance liquid chromatography-tandem mass spectrometry. In: Se Pu. 30 (2), Feb 2012, pp. 154-159. Chinese. PMID 22679829
  9. ↑ A. Navarrete, EG Armitage, M. Musteanu, A. García, A. Mastrangelo, R. Bujak, PP López-Casas, M. Hidalgo, C. Barbas: Metabolomic evaluation of Mitomycin C and rapamycin in a personalized treatment of pancreatic cancer. In: Pharmacol Res Perspect. 2 (6), Dec 2014, p. E00067. PMID 25505613