Vindesine
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| Non-proprietary name | Vindesine | |||||||||||||||||||||
| other names |
3-carbamoyl-4- O- deacetyl-3-de (methoxycarbonyl) -vincaleukoblastine |
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| Molecular formula | C 43 H 55 N 5 O 7 (base) | |||||||||||||||||||||
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| Mechanism of action |
Mitosis inhibitors |
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| Molar mass | 753.936 g mol −1 (base) | |||||||||||||||||||||
| Physical state |
firmly |
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| Melting point |
230–232 ° C (base) |
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| pK s value |
6.04 (base) |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||||||||
Vindesine is a medicinal substance derived from vinblastine , an alkaloid from the rose Catharanthe plant ( Catharanthus roseus , formerly Vinca rosea ). It is a whitish amorphous substance and is used as a chemotherapeutic agent to treat cancer . Vindesine is a cytostatic from the group of mitosis inhibitors.
Mechanism of action
Vindesine inhibits the microtubules (spindle apparatus), which are necessary for the replication of chromosomes (and DNA ). Put simply, the microtubules pull the replicated (doubled) chromosomes (and thus the DNA) apart. The purpose of this is to ensure that each daughter cell receives a complete set of chromosomes when cells are about to divide.
Metabolism
Vindesine follows a 3-compartment model (or 3-phase model) in its metabolism and excretion. The half-life in the first (alpha) phase after administration is 3 minutes, in the second (beta) phase 0.8–1.7 hours and in the third and final (gamma) phase 20–24 hours. The relative volume of distribution is 8.11 l / kg body weight , the absolute 58–600 l. Vindesine does not cross an intact blood-brain barrier and is therefore not detectable in the CSF .
Interactions
- Mitomycin C : If Vindesin is administered to patients with simultaneous or simultaneous administration of mitomycin C, acute bronchospasm with acute dyspnoea may occur, the cause of which is unknown.
- Phenytoin : Vindesin lowers the serum level of phenytoin, whereby its effect is reduced and thus new or increased (epileptic) seizures can occur. This interaction is likely caused by decreased absorption (uptake) of phenytoin from the gastrointestinal tract. An alternative explanation is the increased metabolism (metabolism) of phenytoin. The exact cause of the interaction is not known. As a countermeasure, careful monitoring of serum phenytoin levels and a dose adjustment (increase) of phenytoins are required.
application areas
Vindesine is used as a cytostatic agent to treat cancer . It is not used as an immunosuppressant .
Adults
- Acute lymphoblastic leukemia (ALL).
Children and young people
In children and adolescents, Vindesin is used for:
- Neuroblastoma (NB): Vindesin is used as part of a combination chemotherapy to treat the initial manifestation of neuroblastoma.
- Acute lymphoblastic leukemia : It is used as part of a combination chemotherapy for the treatment of relapse of acute lymphoblastic leukemia.
Application in veterinary medicine
The use of vindesine in combination with cisplatin in dogs with primary lung tumors has been described in isolated cases; anti-tumor activity could be recorded.
administration
Vindesin is given intravenously as an infusion , but it can also be given as a bolus injection .
Due to the poisonous effect of Vindesin in the event of an extravasation, the recommended application site is a vein that does not have any joints in its vicinity that could be damaged by a Vindesin extravasation.
The intrathecal vindesine administration is fatal in most cases.
Side effects
Nausea , vomiting , constipation (constipation), paralytic ileus (intestinal obstruction caused by paralysis), neuropathy (nerve damage).
Abdominal pain caused by intestinal motility disorders is caused by the toxic effects of vindesine on the autonomic nervous system , which is responsible for regulating bowel movement. These abdominal pain can be severe and mostly crampy. As countermeasures, measures to stimulate bowel activity are recommended (especially in the case of simultaneous constipation to prevent ileus) and the administration of butylscopolamine .
Leukopenia with neutropenia and thrombopenia are caused by the inhibitory effect of Vindesin on the rapidly dividing cells of the bone marrow in the course of blood formation . Vindesine blocks the cell division of leukocytes and platelets (and their precursor cells) due to its mechanism of action. Compared to the time of administration, this causes a delay in the decrease in the number of platelets (thrombopenia) and leukocytes (leukopenia) in the peripheral blood. The nadir (low point) occurs 3 to 6 days after administration. Recovery takes place between 7 and 10 days after administration.
Because of the toxic and irritating effects of Vindesin, it may cause irritation and inflammation of the vein ( phlebitis ) through which Vindesin is administered as an infusion or injection. The side effect is less common when injected as a bolus than when given as an infusion. In addition, this side effect is very rare when a central venous catheter is used; it is more common when the vein is small and found on the periphery of the body (such as the back of the hand).
Contraindications
Vindesin must not be used in the presence of severe granulocytopenia or thrombocytopenia , severe bacterial infections, neural muscle atrophy with segmental demyelinating (demyelinating form of Charcot-Marie-Tooth disease ), and hypersensitivity to Vindesin.
Application restrictions
Vindesine can have a mutagenic and teratogenic effect. Therefore, if possible, Vindesin should not be used during pregnancy. Women must not become pregnant during treatment and for up to six months afterwards; men should not father a child during treatment with Vindesin and for up to six months afterwards. Women should not breast-feed during treatment. Due to the immunosuppressive effect of Vindesin, a reduced response to vaccines is to be expected. With live vaccines there is a risk of vaccination damage.
Trade names
Vindesine-containing drugs are commercially available in Germany, Austria and Switzerland under the name Eldisine ( Eli Lilly ).
Web links
- British Columbia Cancer Agency: Vindesine (PDF; 136 kB) Comprehensive, clinically oriented monograph on Vindesine. March 2008, freely accessible.
Individual evidence
- ^ Entry on Vindesin in the DrugBank of the University of Alberta .
- ↑ Entry on Vindesin in the ChemIDplus database of the United States National Library of Medicine (NLM) .
- ↑ a b Data sheet Vindesine sulfate salt hydrate, ≥95% (HPLC) from Sigma-Aldrich , accessed on October 31, 2016 ( PDF ).
- ^ Robert Warren Kirk: Kirk's Current Veterinary Therapy. WB Saunders, 1995, chap. 77, p. 354.
- ↑ a b Technical information Eldisine, as of May 2015.
