Nabumetone
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| Non-proprietary name | Nabumetone | ||||||||||||||||||
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| Molecular formula | C 15 H 16 O 2 | ||||||||||||||||||
| Brief description |
white to almost white, crystalline powder |
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| Molar mass | 228.29 g · mol -1 | ||||||||||||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||||||||
Nabumetone (trade names e.g. Relifex ® , Balmox ® ; manufacturer: GlaxoSmithKline ) is a drug which , as a prodrug, only becomes the active ingredient 6-methoxy-2-naphthylacetic acid (6-MNA) through metabolic conversion in the liver . Like the very similar naproxen , this belongs to the group of non-steroidal anti-inflammatory drugs , which are used for the symptomatic treatment of inflammatory and degenerative rheumatic diseases.
Clinical information
Application areas (indications)
Nabumetone is used for the symptomatic therapy of inflammatory and degenerative rheumatic diseases, such as B. polyarthritis, arthrosis (osteoarthritis), pain and inflammation of the musculoskeletal system.
Contraindications (contraindications)
Nabumetone is contraindicated in patients with known hypersensitivity to the active ingredient, in those who have a history of allergy to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs, gastric and duodenal ulcers (ulcus ventriculi et duodeni). There are no studies on the treatment of children under 14 years of age.
Use during pregnancy and breastfeeding
Like all prostaglandin synthesis inhibitors, nabumetone can have undesirable effects on the fruit in the womb during fetogenesis . It is not known whether nabumetone or its metabolites are excreted in breast milk. Use during pregnancy and breastfeeding is therefore contraindicated.
Special patient groups (diabetics, kidney patients)
In the case of high Qo values, no dose adjustment is necessary in the case of impaired renal function.
Pharmacological properties
Mechanism of action (pharmacodynamics)
Nabumetone is a prodrug (= precursor) and is biotransformed in the organism into the actual active substance, 6-methoxy-2-naphthylacetic acid (6-MNA). Since it is not an acid itself, it belongs to the group of non-steroidal anti-inflammatory drugs that are particularly well tolerated by the stomach. Nabumetone shows a weak inhibition of prostaglandin synthesis, the metabolite, (6-MNA), a somewhat stronger one.
Absorption and distribution in the body (pharmacokinetics)
metabolism
Active metabolites: 6-methoxy-2-naphthylacetic acid (6-MNA)
toxicology
The acute toxicity of nabumetone is very low. Any symptoms of accidental poisoning can be gastrointestinal in nature. There is no specific antidote. Gastric lavage is recommended, followed by oral administration of Carbo medicinalis (1000 mg / kg body weight), divided into several doses.
History
The synthesis of nabumetone was achieved by the British Anthony W. Lake and Carl J. Rose. It was published in 1983 by the Beecham Group (Great Britain) (now GlaxoSmithKline ) as patent US 4,420,639. The patent period expired in 2003.
Presentation and extraction
The synthesis starts from 6-methoxy-2-naphthaldehyde, which is converted in a condensation reaction with acetone . The target compound is then obtained by hydrogenating the condensation product in the presence of palladium- carbon.
Physical Properties
The compound occurs in two polymorphic crystal forms. Polymorph I has a melting point at 80 ° C with a melting enthalpy of 31.3 kJ mol −1 . Polymorph II already melts at 65 ° C with a melting enthalpy of 24.5 kJ mol −1 . Both forms are monotropic to one another. Polymorph I represents the thermodynamically stable form. Both polymorphs form monoclinic crystal lattices with the space group P 2 1 / c (space group no. 14) and differ only in the intermolecular interaction via hydrogen bonds.
Trade names
- Balmox TM (CH)
- Relifex (D, DK)
- Nabuser (I)
literature
- W. Forth, D. Henschler, W. Rummel: General and special pharmacology and toxicology . Ed .: K. Aktories, U. Förstermann, FB Hofmann, K. Starke, U. Förstermann, Walter Rummel. 9th edition. URBAN & FISCHER, Munich 2005, ISBN 3-437-42521-8 .
- E. Mutschler et al. a .: drug effects: textbook of pharmacology and toxicology . 8th edition. Knowledge Verl.-Ges., Stuttgart 2001, ISBN 3-8047-1763-2 .
Individual evidence
- ↑ a b European Pharmacopoeia Commission (ed.): EUROPEAN PHARMACOPOE 5TH EDITION . tape 5.0-5.8 , 2006.
- ↑ a b c d e Price, CP; Crzesiak, AL; Lang, M .; Matzger, AJ: Polymorphism of Nabumetone . In: Crystal Growth & Design 2 (2002) 501-503, doi : 10.1021 / cg0255568 .
- ^ Entry on nabumetone. In: Römpp Online . Georg Thieme Verlag, accessed on May 29, 2014.
- ^ Entry on nabumetone in the ChemIDplus database of the United States National Library of Medicine (NLM) .
- ↑ a b Datasheet Nabumetone from Sigma-Aldrich , accessed on October 16, 2016 ( PDF ).
- ^ A b c d e A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications. 4th edition. Thieme 2001, ISBN 3-13-115134-X .
- ↑ DOSING: Aids for drug use & safety ( Memento from September 10, 2012 in the Internet Archive ).
- ↑ Patent US4420639 : Aromatic compounds. Filed November 12, 1981 , Applicant: Becham Group, Inventor: Anthony W. Lake, Carl J. Rose.
