Lornoxicam
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| Non-proprietary name | Lornoxicam | ||||||||||||||||||
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| Molecular formula | C 13 H 10 ClN 3 O 4 S 2 | ||||||||||||||||||
| Brief description |
Orange-yellow crystals |
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| Molar mass | 371.82 g · mol -1 | ||||||||||||||||||
| Physical state |
firmly |
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| Melting point |
225-230 ° C |
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| pK s value |
4.78 |
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| solubility |
0.0461 mg mL −1 at 25 ° C |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||||||||
Lornoxicam is a nonsteroidal anti-inflammatory drug (NSAID) from the group of oxicams with analgesic , antiphlogistic and antipyretic properties. It is available for oral, parenteral and rectal administration. The medicinal product is intended for the short-term treatment of acute mild to moderately severe pain and symptoms associated with rheumatoid arthritis and osteoarthritis, such as joint pain and inflammation.
Lornoxicam is a chlorinated derivative of tenoxicam with a shorter half-life. The 1979 patent granted to Hoffmann-La Roche names Rudolf Pfister, Paul Zeller, Dieter Binder and Otto Hromatka as inventors. It was developed by the Nycomed subsidiary HN Pharma, and since 1993 it has been in clinical use under the trade name " xefo ". Lornoxicam was marketed in Austria in 1997 and in Germany in 1999.
Extraction
The chlorosulfonation of 2,5-dichlorothiophene with HSO 3 Cl - SOCl 2 gives 2,5-dichlorothiophene-3-sulfonic acid chloride , which is converted into the methyl amide with methylamine in CHCl 3 .
Its carboxylation with butyllithium and CO 2 in ether leads to 5-chloro-3- ( N -methylsulfamoyl) thiophene-2-carboxylic acid, which is esterified with PCl 5 and methanol to give the methyl ester.
This condenses with methyl iodoacetate in the presence of sodium hydride in dimethylformamide to give 5-chloro-3- [ N - (methoxycarbonylmethyl) - N -methylsulfamoyl] thiophene-2-carboxylic acid methyl ester , which with sodium methoxide in methanol gives 6-chloro-4-hydroxy 2-methyl-2 H -thieno [2,3- e ] -1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide is cyclized . Lornoxicam is finally formed
by reaction with 2-aminopyridine .
properties
As with other oxicams, lornoxicam also has keto-enol tautomers :
pharmacology
Pharmacodynamics
The drug blocks prostaglandin synthesis by inhibiting cyclooxygenases ; in addition, it inhibits the release of oxygen radicals by activated leukocytes .
Pharmacokinetics
When administered orally, the peak plasma concentration is reached after about 2 hours. Lornoxicam is metabolized in the liver via cytochrome P450 2C9 with the inactive metabolite 5-hydroxy-lornoxicam at an absorption rate of 90–99% with a short plasma half-life of 3–5 hours for an oxicam . 2/3 of the excretion is hepatic and 1/3 renal .
The protein binding is 99%.
Contraindications
Lornoxicam is not recommended during breastfeeding or pregnancy and must not be taken in the last trimester, as well as in thrombocytopenia , severe heart muscle weakness, gastric ulcer or severely impaired liver / kidney function.
Due to a lack of data, lornoxicam is not recommended for children and adolescents under 18 years of age.
Side effects
Side effects with lornoxicam are similar to those with other NSAIDs, often mild gastrointestinal complaints, nausea, diarrhea and headache. Gastric bleeding , bronchospasm and, very rarely, Stevens-Johnson syndrome are serious but less common . Lornoxicam can affect female fertility.
If the drug is taken continuously for longer than three months, the laboratory values should be checked by a doctor. The body's own opiate peptides dynorphin and beta-endorphin are increasingly released by lornoxicam.
If the maximum daily dose or the maximum duration of intake is exceeded, there is a slightly increased risk of a stroke or heart attack .
Interactions
This medicine must not be taken with other COX-2 inhibitors such as acetylsalicylic acid or ibuprofen . The possible risks include gastric bleeding, poor circulation, and severe damage to the heart, liver, and kidneys. Known interactions exist with, among others, heparin , phenprocoumon , corticosteroids , methotrexate , lithium , pemetrexed , ciclosporin , beta-blockers , diuretics , quinolone antibiotics and sulphonic ureas.
As with piroxicam, cimetidine can increase plasma concentrations, but rarely causes relevant complications.
Trade names
Lornoxicam is commonly sold as a single preparation .
Preparations: Xefo (A, CH), Safem (DK, UK)
See also
Web links
Individual evidence
- ↑ a b c Entry on lornoxicam. In: Römpp Online . Georg Thieme Verlag, accessed on February 11, 2016.
- ↑ a b Manufacturing process at drugfuture (English).
- ↑ a b Entry on lornoxicam in the Human Metabolome Database (HMDB) , accessed on 2016-02-19.
- ↑ a b Entry on lornoxicam in the DrugBank of the University of Alberta .
- ↑ a b Lornoxicam data sheet from Sigma-Aldrich , accessed on February 11, 2016 ( PDF ).
- ↑ a b c d e package insert from xefo , accessed February 2016.
- ↑ a b Patent application DE2838851 : Thiazine derivatives. Registered on August 31, 1978 , published on December 25, 1979 , Applicant: Hoffmann-La Roche Inc, Inventors: Rudolf Pfister, Paul Zeller, Dieter Binder, Otto Hromatka.
- ^ History of Lornoxicam at Nycomed , accessed February 2016.
- ↑ Nycomed files for Lornoxicam at pharmaletter.com (English), accessed on February 24, 2016.
- ^ Institute for Health and Social Research GmbH: Analog active ingredients in the drug market: Therapeutic use and importance for health insurance expenses (PDF), Structural Research in Health Care Volume 30, pp. 138f, Berlin 2001. ISBN 3-9808407-1-9 . Retrieved February 26, 2016.
- ↑ a b Haberfeld, H (Ed.): Austria Codex , 2009/2010. Edition, Österreichischer Apothekerverlag, Vienna 2009, ISBN 3-85200-196-X .
- ↑ Lornoxicam pharma criticism at infomed, 2003.
- ↑ W. Kullich, G. Klein: The distribution of the body's opiate peptides dynorphin and β-endorphin under the influence of non-steroidal anti-inflammatory drug Lornoxicam iv In: Current Rheumatology. 17, 1992, p. 128, doi : 10.1055 / s-2008-1047362 .
- ↑ Godara Sushila, Srivastava R, Godara Rajesh, Bhutani Garima: Lornoxicam: a review of its therapeutic potential in different clinical studies . In: Journal of Drug Delivery & Therapeutics; 2013, 3 (2), 145-148.
- ↑ Klopp, T (Ed.): Arzneimittel-Interaktion , 2010/2011. Edition, Working Group for Pharmaceutical Information, 2010, ISBN 978-3-85200-207-1 .
- ↑ Drugs.com International: Lornoxicam (English).
