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| Clinical data | |
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| Trade names | Clinoril |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a681037 |
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| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
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| Pharmacokinetic data | |
| Bioavailability | Approximately 90% (Oral) |
| Metabolism | ? |
| Eliminationhalf-life | 7.8 hours, metabolites up to 16.4 hours |
| Excretion | Renal (50%) and fecal (25%) |
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| DrugBank |
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| ChemSpider |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.048.909 |
| Chemical and physical data | |
| Formula | C20H17FO3S |
| Molar mass | 356.41 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 182 to 185 °C (360 to 365 °F) (decomp.) |
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Sulindac is anonsteroidal anti-inflammatory drug (NSAID) of the arylalkanoic acid class that is marketed asClinoril. Imbaral (not to be confused withmebaral) is another name for this drug. Its name is derived from sul(finyl)+ ind(ene)+ ac(etic acid)It was patented in 1969 and approved for medical use in 1976.[1]
Like other NSAIDs, it is useful in the treatment ofacute orchronicinflammatory conditions. Sulindac is aprodrug, derived fromsulfinylindene, that is converted in the body to the active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide that is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAIDs except for drugs of theCOX-2 inhibitor class.[2] The exact mechanism of its NSAID properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibitingprostaglandin synthesis.
Its usualdosage is 150-200milligrams twice per day, with food. It should not be used by persons with a history of major allergic reactions (urticaria oranaphylaxis) toaspirin or other NSAIDs, and should be used with caution by persons having pre-existingpeptic ulcer disease. Sulindac is much more likely than other NSAIDs to cause damage to the liver or pancreas, though it is less likely to cause kidney damage than other NSAIDs.
Sulindac seems to have a property, independent of COX-inhibition, of reducing the growth of polyps and precancerous lesions in the colon, especially in association withfamilial adenomatous polyposis, and may have other anti-cancer properties.[3][4]
In October 2020, the U.S.Food and Drug Administration (FDA) required thedrug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.[5][6] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.[5][6]
In September 2010 a federal jury in New Hampshire awarded $21 million to Karen Bartlett, a woman who developedStevens–Johnson syndrome/Toxic epidermal necrolysis as a result of taking a generic brand of sulindac manufactured by Mutual Pharmaceuticals for her shoulder pain. Ms. Bartlett sustained severe injuries including the loss of over 60% of her surface skin and permanent near-blindness. The case had been appealed to the United States Supreme Court, where the main issue was whether federal law preempts Ms. Bartlett's claim.[7] On June 24, 2013, the Supreme Court ruled 5–4 in favor of Mutual Pharmaceuticals, throwing out the earlier $21 million jury verdict.[8][9]
Rxn ofp-fluorobenzyl chloride (1) with the anion of diethylmethyl malonate (2) gives intermediate diester (3), saponification of which and subsequent decarboxylation leads to4. {Alternatively it can be formed byPerkin reaction between p-fluorobenzaldehyde andpropionic anhydride in the presence ofNaOAc, followed bycatalytic hydrogenation of the olefinic bond using a palladium on carbon catalyst.}
Polyphosphoric acid (PPA) cyclization leads to 5-fluoro-2-methyl-3-indanone (4). AReformatsky reaction withzincamalgam and bromoacetic ester leads to carbinol (5), which is then dehydrated withtosic acid to indene6. {Alternatively, this step can be performed in aKnoevenagel condensation withcyanoacetic acid, which is then further decarboxylated.}
The active methylene group is condensed withp-methylthiobenzaldehyde, usingsodium methoxide as catalyst, and then saponified to giveZ (7) which in turn oxidized withsodium metaperiodate to sulfoxide8, theantiinflammatory agent sulindac.
This article incorporates text from this source, which is in thepublic domain. This article incorporates text from this source, which is in thepublic domain.| pyrazolones / pyrazolidines | |
|---|---|
| salicylates | |
| acetic acid derivatives and related substances | |
| oxicams | |
| propionic acid derivatives (profens) |
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| n-arylanthranilic acids (fenamates) | |
| COX-2 inhibitors (coxibs) | |
| other | |
| NSAID combinations | |
Key:underline indicates initially developed first-in-class compound of specific group;#WHO-Essential Medicines;†withdrawn drugs;‡veterinary use. | |
