Simvastatin

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Structural formula
Simvastatin structural formula
General
Non-proprietary name Simvastatin
other names
  • (1 S , 3 R , 7 S , 8 S , 8 aR ) -8- {2 - [(2 R , 4 R ) -4-hydroxy-6-oxooxan-2-yl] ethyl} -3,7- dimethyl 1,2,3,7,8,8a-hexahydronaphthalen-1-yl-2,2-dimethylbutanoate ( IUPAC )
Molecular formula C 25 H 38 O 5
External identifiers / databases
CAS number 79902-63-9
EC number 616-751-8
ECHA InfoCard 100.115.749
PubChem 54454
DrugBank DB00641
Wikidata Q670131
Drug information
ATC code
Drug class

Statins

Mechanism of action

HMG-CoA reductase - inhibitor

properties
Molar mass 418.57 g · mol -1
Physical state

firmly

Melting point

127-132 ° C

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
Toxicological data

4438 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 .

Simvastatin is the non-proprietary name of a drug from the group of statins that is used as a cholesterol-lowering drug .

Simvastatin is structurally derived from the naturally occurring monacolin K ( lovastatin ).

Mechanism of action

Simvastatin is an HMG-CoA reductase inhibitor. The HMG-CoA reductase acts as a catalyst in the reduction of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, which is a limiting step in the hepatic cholesterol synthesis. By lowering the cholesterol synthesis, the liver cells increase the number of LDL receptors on the cell surface, so that the LDL uptake into the liver cell increases and thus the LDL level in the blood is reduced.

Absorption and distribution in the body

After ingestion, the active ingredient is mainly metabolized by the cytochrome P450 3A4 , therefore CYP – 3A4– inhibitors such as ketoconazole , itraconazole and clarithromycin or grapefruit juice should not be taken together with simvastatin.

Side effects

Simvastatin has the usual side effects of this group of active substances , such as upper abdominal discomfort, increased transaminases and myopathies such as rhabdomyolysis .

Manufacturing

It is produced partially synthetically from lovastatin , with its 2-methylbutanoyl side chain being transesterified to give the 2,2-dimethylbutanoyl radical.

A multi-step synthesis for simvastatin is described in the literature.

Forms of trade

Simvastatin was launched in Germany in 1990 by MSD Sharp & Dohme as Zocor . In May 2003 the patent on the active ingredient expired. Since then, simvastatin has also been produced and sold by various generic manufacturers. Tablets are available in doses of 5, 10, 20, 30, 40, 60 and 80 mg.

Monopreparations

Zocor (D, CH), Zocord (A), numerous generics (D, A, CH)

Combination preparations

with ezetimibe : Inegy (D, A, CH), Goltor

Web links

Individual evidence

  1. ↑ a b c d data sheet Simvastatin from Sigma-Aldrich , accessed on June 13, 2011 ( PDF ).Template: Sigma-Aldrich / name not given
  2. ↑ Information from Merck (PDF; 166 kB).
  3. ↑ Richard Daikeler, idols Use, Sylke Waibel: diabetes. Evidence-based diagnosis and therapy. 10th edition. Kitteltaschenbuch, Sinsheim 2015, ISBN 978-3-00-050903-2 , p. 149.
  4. ↑ K. Hardtke et al. (Ed.): Commentary on the European Pharmacopoeia Ph. Eur. 6.4, Simvastatin. Loose-leaf collection, 34th delivery 2010, Wissenschaftliche Verlagsgesellschaft Stuttgart.
  5. ^ Axel Kleemann , Jürgen Engel, Bernd Kutscher and Dietmar Reichert: Pharmaceutical Substances, 4th edition (2000), 2 volumes published by Thieme-Verlag Stuttgart, ISBN 978-1-58890-031-9 ; online since 2003 with biannual additions and updates.
  6. ↑ Red List online, as of September 2009.
  7. ↑ AM comp. d. Switzerland, as of September 2009.
  8. ↑ AGES-PharmMed, as of September 2009.