Mitomycin C
Structural formula | ||||||||||||||||||||||
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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 |
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Molecular formula | C 15 H 18 N 4 O 5 | |||||||||||||||||||||
Brief description |
blue-purple odorless powder |
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Drug information | ||||||||||||||||||||||
ATC code | ||||||||||||||||||||||
Drug class |
Cytostatics |
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properties | ||||||||||||||||||||||
Molar mass | 334.33 g · mol -1 | |||||||||||||||||||||
Melting point |
> 360 ° C |
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pK s value |
10.9 |
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solubility | ||||||||||||||||||||||
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Toxicological data | ||||||||||||||||||||||
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 |
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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)
- Anal cancer (combined with 5-fluorouracil , as part of chemoradiotherapy)
- Bladder cancer ( mitomycin C dissolved in sodium chloride solution is instilled into the bladder via a catheter )
- Stomach , lung , pancreas , colon , breast , liver cell , cervical , esophageal cancer
- Head and neck cancer
- Osteosarcoma
- Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
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
Amétycine (D), Mitem (D), Urocin (D), Mito-medac (D), various generics (D, A)
Individual evidence
- ↑ a b Mitomycin C data sheet (PDF) from Carl Roth , accessed on February 24, 2013.
- ↑ a b Entry on Mitomycins. In: Römpp Online . Georg Thieme Verlag, accessed on July 1, 2019.
- ↑ a b c Entry on Mitomycin C in the GESTIS substance database of the IFA , accessed on January 23, 2020(JavaScript required) .
- ↑ Mitomycins - Lexicon of Biology. In: Spektrum.de. March 27, 2014, accessed May 4, 2015 .
- ↑ 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.
- ↑ pharmische-zeitung.de: Surgical treatment of eye diseases (accessed on January 3, 2017)
- ^ DAC / NRF , 2012.
- ^ 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
- ↑ 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