Etodolac, a novel antiinflammatory agent. The syntheses and biological evaluation of its metabolites

Humber, Leslie G.; Ferdinandi, E. S.; Demerson, Christopher A.; Ahmed, Syed Waseemuddin; Shah, Uresh; Mobilio, Dominick; Sabatucci, Joseph P.; Lange, Barbara De; Labbadia, Francesco

doi:10.1021/jm00117a009

Cited by 38 publications

(14 citation statements)

References 5 publications

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“…2‐Iodophenyl‐hydrazine hydrochloride ( 3⋅HCl ) was obtained according to a literature protocol in 60 % yield as colourless solid after recrystallization from MeOH/Et 2 O: m.p. 160–161 °C; lit .…”

Section: Methodsmentioning

confidence: 62%

Magnetostructural Investigation of Orthogonal 1‐Aryl‐3‐Phenyl‐1,4‐Dihydrobenzo[e][1,2,4]triazin‐4‐yl Derivatives

Gardias

Kaszyński

Obijalska

et al. 2017

Chemistry A European J

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3-Phenyl-1,4-dihydrobenzo[e][1,2,4]triazinyl radicals with the N(1) position substituted with naphth-2-yl (1 b), naphth-1-yl (1 c), pyren-1-yl (1 d), anthracen-9-yl (1 e), 2-trifluoromethylphenyl (1 f), 3-trifluoromethylphenyl (1 g), and 2-iodophenyl (1 h) were characterized by using single-crystal X-ray diffraction, variable-temperature magnetic susceptibility, and DFT computational methods. The substituent at N(1) is essentially orthogonal to the heterocycle plane in 1 f and 1 h, and with a high torsion angle in 1 c and 1 d. Radicals 1 c and 1 h form unusual infinite chains with crisscrossing hetero-co-facial π-π interactions, whereas radical 1 d forms analogous homo-co-facial arrangements. Infinite chains of homo-co-facial π-π dimers are found in 1 b, 1 f and 1 g; in the latter the position of the CF group controls the slippage of the dimers in the chain. No π-π parallel arrangements were found in 1 e. Magnetic susceptibility measurements demonstrated strong antiferromagnetic interactions in 1 b (J=-264±4 cm ) and 1 f (J=-134±1 cm ), while weak intradimer ferromagnetic interactions were found in 1 g (J =+21±1 and J =-15±1 cm ). Other derivatives exhibit typical weak antiferromagnetic exchange interactions in a range of -5 to -10 cm .

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Section: Methodsmentioning

confidence: 62%

Magnetostructural Investigation of Orthogonal 1‐Aryl‐3‐Phenyl‐1,4‐Dihydrobenzo[e][1,2,4]triazin‐4‐yl Derivatives

Gardias

Kaszyński

Obijalska

et al. 2017

Chemistry A European J

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“…Substances present in HPLC peaks corresponding to etodolac glucuronide and 6‐OH etodolac glucuronide promoted binding of the antibody to RBCs. Etodolac is known to be excreted mainly in the form of glucuronide conjugates with or without hydroxylation at positions 6, 7, and 8 13,14 . As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Immune hemolytic anemia caused by sensitivity to a metabolite of etodolac, a nonsteroidal anti‐inflammatory drug

et al. 2000

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This patient appears to have experienced acute, severe immune hemolytic anemia on two occasions because of sensitivity to the glucuronides of etodolac and 6-OH etodolac. In patients suspected of having drug-induced immune hemolytic anemia, RBC-reactive antibodies can sometimes be detected by using urine from an individual taking the implicated medication as the source of drug metabolites in in vitro reactions. For patients who present with acute immune hemolysis, a careful history of drug exposure should be taken, and, where indicated, confirmatory testing should be performed to identify the sensitizing drug and prevent inadvertent reinduction of hemolysis at a later time.

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“…6 Nonsteroidal anti-inflammatory drugs (NSAIDs)-both the inhibitors of the cyclooxygenase (COX) enzyme type 1 and the inhibitors of the enzyme COX-2-were identified as a cause of drug-induced immune cytopenia, and also cases of intravascular hemolysis and acute renal failure. [7][8][9][10][11][12][13] Etoricoxib, the drug used in the case we report here, is an NSAID that is a highly selective inhibitor of COX-2. It is usually prescribed to treat osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis as an alternative to traditional NSAIDs in refractory cases.…”

Section: Discussionmentioning

confidence: 99%

Etoricoxib‐induced immune hemolytic anemia: first case presenting acute kidney failure

et al. 2019

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BACKGROUND Etoricoxib is a selective inhibitor of cyclooxygenase 2 used mainly to treat osteoarticular pain. Here, we report the case of a patient who developed acute kidney failure and immune hemolytic anemia after the use of etoricoxib. STUDY DESIGN AND METHODS An 83‐year‐old female patient developed immune hemolytic anemia and acute kidney failure after treatment with etoricoxib for articular pain. Given the acute kidney failure, she required five hemodialysis sessions. She was discharged after 17 days. The case of immune hemolytic anemia and kidney failure was fully resolved. RESULTS The direct antiglobulin test was not only positive for IgG but also for C3b and C3d, showing a very intense reactivity (++++). The eluate's reactivity was weaker (++) and showed no defined specificity. The investigation of unexpected antibodies in the serum of the patient showed a reactivity pattern similar to the eluate's: weak reactivity without specificity. The serum of the patient was compared to urine and plasma samples of two groups of volunteers. The indirect antiglobulin test showed only a very strong reactivity with the urine samples of the volunteers who had received etoricoxib. DISCUSSION Considering that positive eluate is not the typical serologic profile of drug‐induced immune hemolytic anemia, developing in‐house techniques to show the causal link between them may be of interest to guide the treatment and avoid the empirical use of drugs. CONCLUSION Etoricoxib must be considered as a possible cause of acute kidney failure in cases of immune hemolytic anemia.

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Etodolac, a novel antiinflammatory agent. The syntheses and biological evaluation of its metabolites

Cited by 38 publications

References 5 publications

Magnetostructural Investigation of Orthogonal 1‐Aryl‐3‐Phenyl‐1,4‐Dihydrobenzo[e][1,2,4]triazin‐4‐yl Derivatives

Magnetostructural Investigation of Orthogonal 1‐Aryl‐3‐Phenyl‐1,4‐Dihydrobenzo[e][1,2,4]triazin‐4‐yl Derivatives

Immune hemolytic anemia caused by sensitivity to a metabolite of etodolac, a nonsteroidal anti‐inflammatory drug

Etoricoxib‐induced immune hemolytic anemia: first case presenting acute kidney failure

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