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Sulindac

술린다크 C화학적 특성, 용도, 생산

개요

Many non-steroidal anti-inflammatory drugs (NSAIDs) are potent but non-selective inhibitors of both COX-1 and COX-2 in humans. Sulindac is one of the older NSAIDs, an isostere of indomethacin developed before the inducible form of COX-2 was discovered. Although a number of NSAIDs have been found to protect against digestive tract cancers, sulindac has an extensive epidemiology documenting reduced human colorectal cancer. In murine models, sulindac was found not only to inhibit the enzymatic activity of polyp-associated COX-2, but also to downregulate the expression of colonic COX-2 protein to control levels.

화학적 성질

Yellow Crystalline Solid

용도

Sulindac is a non-steroidal anti-inflammatory drug.

정의

ChEBI: A monocarboxylic acid that is 1-benzylidene-1H-indene which is substituted at positions 2, 3, and 5 by methyl, carboxymethyl, and fluorine respectively, and in which the phenyl group of the benzylidene moiety is substituted at the ara position by a methylsulfinyl group. It is a prodrug for the corresponding sulfide, a non-steroidal anti-inflammatory drug, used particularly in the treatment of acute and chronic inflammatory conditions.

Indications

Sulindac (Clinoril) is chemically related to indomethacin and is generally used for the same indications. It is a prodrug that is metabolized to an active sulfide metabolite and an inactive metabolite. The most frequently reported side effects are GI pain, nausea, diarrhea, and constipation. The incidence of these effects is lower than for indomethacin, presumably because sulindac is a prodrug and thus the active metabolite is not highly concentrated at the gastric mucosa. As with indomethacin, a rather high incidence of CNS side effects (dizziness, headache) also occurs.

일반 설명

Sulindac, (Z)-5-fluoro-2-methyl-1-([p-(methylsulfinyl)phenyl]methylene)-1H-indene-3-acetic acid (Clinoril), isan NSAID prodrug that contains a chiral sulfoxide moietybut is marketed as the racemate because it undergoes invivo reduction by the hepatic enzymes into its achiral, activemetabolite, methyl sulfide that exhibits potent andnonselective COX inhibition similar to indomethacin.
The parent sulfoxide has a plasma half-life of 8 hours, andthe active methyl sulfide metabolite is 16.4 hours. The morepolar and inactive sulfoxide is virtually the only form excretedinto the renal tubules, thus sulindac is believed to haveminimal nephrotoxicity associated with indomethacin. Thelong half-life of sulindac is caused by the extensive enterohepaticcirculation and reactivation of the inactive sulfoxideexcreted. Coadministration of aspirin is contraindicated becauseit considerably reduces the sulfide blood levels. Carefulmonitoring of patients with a history of ulcers is recommended.Gastric bleeding, nausea, diarrhea, dizziness, andother adverse effects have been noted with sulindac, but witha lower frequency than with aspirin. Sulindac is recommendedfor RA, OA, and ankylosing spondylitis.

생물학적 활성

Prodrug. Metabolizes to sulindac sulfide, a cyclooxgenase inhibitor that represses ras signaling, and sulindac sulfone, an antitumor agent, following oral administration in vivo . Widely used anti-inflammatory agent.

Pharmacokinetics

Sulindac is well absorbed on oral administration (90%), reaches peak plasma levels within 2 to 4 hours, and being acidic (pKa = 4.5), is highly bound to serum proteins (93%). The metabolism of sulindac plays a major role in its actions, because all of the pharmacological activity is associated with its major metabolite. Sulindac is, in fact, a pro-drug, the sulfoxide function being reduced to the active sulfide metabolite. Sulindac is absorbed as the sulfoxide, which is not an inhibitor of prostaglandin biosynthesis in the GI tract. Prostaglandins exert a protective effect in the GI tract, and inhibition of their synthesis here leads to many of the GI side effects noted for most NSAIDs. Once sulindac enters the circulatory system, it is reduced to the sulfide, which is an inhibitor of prostaglandin biosynthesis in the joints. Thus, sulindac produces less GI side effects, such as bleeding, ulcerations, and so on, than indomethacin and many other NSAIDs. In addition, the active metabolite has a plasma half-life approximately twice that of the parent compound (～16 hours versus 8 hours), which favorably affects the dosing schedule. In addition to the sulfide metabolite, sulindac is oxidized to the corresponding sulfone, which is inactive. A minor product results from hydroxylation of the benzylidene function and the methyl group at the 2-position. Glucuronides of several metabolites also are found. Sulindac as well as the sulfide and the sulfone metabolites are all highly protein-bound. Despite the fact that the sulfide metabolite is a major activation product and is found in high concentration in human plasma, it is not found in human urine, perhaps because of its high degree of protein binding.

Clinical Use

Sulindac is indicated for long-term use in the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and acute gouty arthritis. The usual maximum dosage is 400 mg/day, with starting doses recommended at 150 mg twice a day. It is recommended that sulindac be administered with food.

부작용

Whereas the toxicity of sulindac is lower than that observed for indomethacin and other NSAIDs, the spectrum of adverse reactions is very similar. The most frequent side effects reported are associated with irritation of the GI tract (e.g., nausea, dyspepsia, and diarrhea), although these effects generally are mild. Effects on the CNS (e.g., dizziness and headache) are less common. Dermatological effects are less frequently encountered.

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공급자	전화	이메일	국가	제품 수	이점
Hebei Mojin Biotechnology Co., Ltd	+8613288715578	sales@hbmojin.com	China	12456	58
Xiamen Wonderful Bio Technology Co., Ltd.	+8613043004613	Sara@xmwonderfulbio.com	China	305	58
Capot Chemical Co.,Ltd.	571-85586718 +8613336195806	sales@capotchem.com	China	29797	60
Shanghai Bojing Chemical Co.,Ltd.	+86-86-02137122233 +8613795318958	bj1@bj-chem.com	China	298	55
Henan Tianfu Chemical Co.,Ltd.	+86-0371-55170693 +86-19937530512	info@tianfuchem.com	China	21691	55
Nanjing ChemLin Chemical Industry Co., Ltd.	025-83697070	product@chemlin.com.cn	CHINA	3012	60
ATK CHEMICAL COMPANY LIMITED	+undefined-21-51877795	ivan@atkchemical.com	China	32480	60
Shanghai Zheyan Biotech Co., Ltd.	18017610038	zheyansh@163.com	CHINA	3620	58
career henan chemical co	+86-0371-86658258	sales@coreychem.com	China	29914	58
Hebei Guanlang Biotechnology Co., Ltd.	+86-19930503282	alice@crovellbio.com	China	8823	58

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