Etodolac

Bezeichnung:Etodolac

CAS-Nr41340-25-4

Englisch Name:Etodolac

CBNumberCB3216064

SummenformelC17H21NO3

Molgewicht287.35

MOL-Datei41340-25-4.mol

Etodolac physikalisch-chemischer Eigenschaften

Schmelzpunkt	145-1480C
Siedepunkt	507.9±45.0 °C(Predicted)
Dichte	1.193±0.06 g/cm3(Predicted)
storage temp.	2-8°C
Löslichkeit	Practically insoluble in water, freely soluble in acetone and in ethanol (96 per cent)
pka	4.65(at 25℃)
Aggregatzustand	Solid
Farbe	White to Orange to Green
Wasserlöslichkeit	40mg/L(37 ºC)
Merck	14,3874
BCS Class	2
InChIKey	NNYBQONXHNTVIJ-QGZVFWFLSA-N
CAS Datenbank	41340-25-4(CAS DataBase Reference)
EPA chemische Informationen	Pyrano[3,4-b]indole-1-acetic acid, 1,8-diethyl-1,3,4,9-tetrahydro- (41340-25-4)

Sicherheit

Kennzeichnung gefährlicher	T,Xi
R-Sätze:	23/24/25-40-36-25-36/37/38
S-Sätze:	22-36-45-26-36/37
RIDADR	3249
WGK Germany	3
RTECS-Nr.	UQ0360000
HazardClass	6.1(b)
PackingGroup	III
HS Code	29349990

Gefahreninformationscode (GHS)

Etodolac Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R23/24/25:Giftig beim Einatmen, Verschlucken und Berührung mit der Haut.
R40:Verdacht auf krebserzeugende Wirkung.
R36:Reizt die Augen.
R25:Giftig beim Verschlucken.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S22:Staub nicht einatmen.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36/37:Bei der Arbeit geeignete Schutzhandschuhe und Schutzkleidung tragen.
Beschreibung
Etodolac (etodolic acid) is a non-steroidal antiinflammatory/analgesic agent useful in the treatment of various inflammatory conditions, including rheumatoid and osteoarthritis.
Chemische Eigenschaften
Crystalline Solid
Originator
Ayerst (USA)
Verwenden
For acute and long-term management of signs and symptoms of osteoarthritis and rheumatoid arthritis, as well as for the management of pain.
Verwenden
betaadrenergic agonist
Verwenden
Etodolac is a non-steroidal anti-inflammatory drug (NSAID). Product Data Sheet
Verwenden
Etodolac is a non-steroidal anti-inflammatory drug (NSAID) that selectively inhibits cyclooxygenase-2 (COX-2). Etodolac displays anti-inflammatory effects in both adjuvant arthritic and normal rats. E todolac is an anti-inflammatory; analgesic.
Definition
ChEBI: A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is substituted by a 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl moiety. A preferential inhibitor of cyclo-oxygenase 2 and non-steroidal anti-inflammatory, it is used for the treatment of rheumatoid arthritis and osteoarthritis, and for the alleviation of postoperative pain. Administered as the racemate, only the (S)-enantiomer is active.
Indications
Etodolac (Lodine) is indicated for the treatment of osteoarthritis, rheumatoid arthritis, and acute pain. It inhibits COX-2 with slightly more selectivity than COX-1 and therefore produces less GI toxicity than many other NSAIDs. Common adverse effects include skin rashes and CNS effects.
Trademarks
Lodine(Wyeth).
Allgemeine Beschreibung
Etodolac (Lodine, Ultradol), a chiral, COX-2 selectiveNSAID drug that is marketed as a racemate, possesses an indolering as the aryl portion of this group of NSAID drugs.It shares many similar properties of this group and is indicatedfor short- and long-term management of pain and OA.
Similar to ketorolac, etodolac exhibits several uniqueenantioselective pharmacokinetic properties. For example,the “inactive” (R)-enantiomer has approximately a 10-foldhigher plasma concentration than the active (S)-enantiomer.Furthermore, the active (S)-enantiomer is less protein boundthan its (R)-enantiomer and therefore has a very large volumeof distribution. It is well absorbed with an elimination halflifeof 6 to 8 hours. Etodolac is extensively metabolized intothree major inactive metabolites, 6-hydroxy etodolac (via aromatichydroxylation), 7-hydroxy-etodolac (via aromatic hydroxylation),and 8-(1'-hydroxylethyl) etodolac (via benzylichydroxylation), which are eliminated as the correspondingether glucuronides. Its unstable, acyl glucuronide, however,is subject to enterohepatic circulation and reactivation tothe parent drug, similar to other NSAIDS in this class.
Biologische Aktivität
Non-steroidal anti-inflammatory drug (NSAID) that selectively inhibits cyclooxygenase-2 (COX-2) (IC 50 values are 53 and >100 μ M for COX-2 and COX-1 respectively). Displays anti-inflammatory effects in both adjuvant arthritic and normal rats.
Biochem/physiol Actions
Non-steroidal anti-inflammatory compound that is a non-selective inhibitor of COX-1 and COX-2.
Mechanism of action
The primary mechanism of action appears to be inhibition of the biosynthesis of prostaglandins at the cyclooxygenase step, with no inhibition of the lipoxygenase system. Etodolac, however, possesses a more favorable ratio of inhibition of prostaglandin biosynthesis in human rheumatoid synoviocytes and chondrocytes than by cultured human gastric mucosal cells compared to ibuprofen, indomethacin, naproxen, diclofenac, and piroxicam.
Pharmakokinetik
Etodolac is rapidly absorbed following oral administration, with maximum serum levels being achieved within 1 to 2 hours, and it is highly bound to plasma proteins (99%) with pKa 4.7. The penetration of etodolac into synovial fluid is greater than or equal to that of tolmetin, piroxicam, or ibuprofen. Only diclofenac appears to provide greater penetration.
Clinical Use
Etodolac is promoted as the first of a new chemical class of anti-inflammatory drugs, the pyranocarboxylic acids. Although not strictly an arylacetic acid derivative (because there is a two-carbon atom separation between the carboxylic acid function and the hetero-aromatic ring), it still possesses structural characteristics similar to those of the heteroarylacetic acids and is classified here. It was introduced in the United States in 1991 for acute and long-term use in the management of osteoarthritis and as an analgetic. It also possesses antipyretic activity. Etodolac is marketed as a racemic mixture, although only the S-(+)-enantiomer possesses anti-inflammatory activity in animal models. Etodolac also displays a high degree of enantioselectivity in its inhibitory effects on the arachidonic acid cyclooxygenase system.
Veterinary Drugs and Treatments
Etodolac is labeled for the management of pain and inflammation associated with osteoarthritis in dogs. It may find uses, however, for a variety of conditions where pain and/or inflammation should be treated.
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
ACE inhibitors and angiotensin-II antagonists: antagonism of hypotensive effect, increased risk of nephrotoxicity and hyperkalaemia
Analgesics: avoid concomitant use of 2 or more NSAIDs, including aspirin (increased side effects); avoid with ketorolac, increased risk of side effects and haemorrhage.
Antibacterials: possibly increased risk of convulsions with quinolones.
Anticoagulants: effects of coumarins and phenindione enhanced; possibly increased risk of bleeding with heparin, dabigatran and edoxaban - avoid long term use with edoxaban.
Antidepressants: increased risk of bleeding with SSRIs and venlafaxine.
Antidiabetic agents: effects of sulphonylureas enhanced.
Antiepileptics: possibly increased phenytoin concentration.
Antivirals: increased risk of haematological toxicity with zidovudine; concentration possibly increased by ritonavir
Ciclosporin: may potentiate nephrotoxicity
Cytotoxic agents: reduced excretion of methotrexate; increased risk of bleeding with erlotinib.
Diuretics: increased risk of nephrotoxicity; antagonism of diuretic effect; hyperkalaemia with potassium-sparing diuretics.
Lithium: excretion decreased.
Pentoxifylline: increased risk of bleeding
Tacrolimus: increased risk of nephrotoxicity.
Stoffwechsel
Etodolac is metabolized to three hydroxylated metabolites and to glucuronide conjugates, none of which possesses important pharmacological activity. Metabolism appears to be the same in the elderly as in the general population, so no dosage adjustment appears necessary. Etodolac is indicated for the management of the signs and symptoms of osteoarthritis and for the management of pain.
Einzelnachweise
[1] kumagai k1, kubo m, imai s, toyoda f, maeda t, okumura n, matsuura h, matsusue y.the cox-2 selective blocker etodolac inhibits tnfα-induced apoptosis in isolated rabbit articular chondrocytes. int j mol sci. 2013 sep 30;14(10):19705-15.
[2] hakozaki m1, hojo h, kikuchi s, abe m. etodolac, a selective cyclooxygenase-2 inhibitor, induces apoptosis by activating caspases in human malignant rhabdoid tumor cells (frtk-1). oncol rep. 2007 jan;17(1):169-73.

Etodolac Upstream-Materialien And Downstream Produkte

Etodolac Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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