Tolmetin
(Synonyms: 托麦汀；托美丁) 目录号 : GC61337
Tolmetin (Tolectin) is a nonsteroidal anti-inflammatory drug of the heterocyclic acetic acid derivative class and also exhibits analgesic and antipyretic activity.
Cas No.:26171-23-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tolmetin (Tolectin) is a nonsteroidal anti-inflammatory drug of the heterocyclic acetic acid derivative class and also exhibits analgesic and antipyretic activity.
| Cas No. | 26171-23-3 | SDF | |
| 别名 | 托麦汀；托美丁 | ||
| Canonical SMILES | O=C(O)CC1=CC=C(C(C2=CC=C(C)C=C2)=O)N1C | ||
| 分子式 | C15H15NO3 | 分子量 | 257.28 |
| 溶解度 | DMSO: 100 mg/mL (388.68 mM) | 储存条件 | 4°C, away from moisture |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.8868 mL | 19.4341 mL | 38.8682 mL |
| 5 mM | 0.7774 mL | 3.8868 mL | 7.7736 mL |
| 10 mM | 0.3887 mL | 1.9434 mL | 3.8868 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Absorption and excretion of Tolmetin in arthritic patients
Clin Pharmacol Ther 1979 Jul;26(1):122-8.PMID:445955DOI:10.1002/cpt1979261122.
The absorption, kinetics, biotransformation, and excretion of Tolmetin and its metabolites were studied in patients with rheumatoid arthritis (RA) to evaluate the effects of the disease on Tolmetin disposition. Five RA patients were stabilized on Tolmetin sodium (300 mg, 4 times daily for 14 days) before receiving a single oral solution dose of tolmetin-14C sodium (300 mg as the acid) on day 15. Tolmetin was rapidly and completely absorbed (peak time, 20 to 60 min) and eliminated rapidly from plasma with a biphasic decay curve (t1/2beta congruent to 2.1 hr). MCPA, the oxidative metabolite, appeared more slowly (peak time, 40 to 90 min) but was eliminated rapidly in a biphasic manner (t1/2beta congruent to 1.7 hr). The terminal elimination phases for both Tolmetin and MCPA demonstrated a curvature which suggested possible nonlinearity in the kinetic disposition of the drug. There were no apparent effects of the disease on the kinetics of Tolmetin or MCPA. Tolmetin, MCPA, and Tolmetin glucuronide were recovered quantitatively in urine (0 to 72 hr) with most of the exretion occurring in the 0- to 24-hr period. A significant increase, relative to data on normal subjects, in the renal clearance of both Tolmetin and MCPA was noted. Concomitant increase in the apparent volume of distribution secondary to reported decreases in the plasma protein binding of Tolmetin appeared to be the reason for increased renal clearance of Tolmetin.
Protein binding of Tolmetin
Clin Pharmacol Ther 1978 Dec;24(6):694-705.PMID:710027DOI:10.1002/cpt1978246694.
The protein binding of the new nonsteroidal anti-inflammatory agent Tolmetin to human serum albumin (HSA) and to the plasma of 8 healthy subjects was studied by equilibrium dialysis at 37 degrees and pH 7.4 with 14C-tolmetin. Over the total concentration (Ct) range 3.0 to 28.7 microgram/ml (therapeutic range), the fraction of Tolmetin unbound to 4% HSA was largely invariant at 0.3%. At 100 microgram/ml the unbound fraction rose to 0.8 and at 434 microgram/ml to 3.6%. Within the therapeutic concentration range, Tolmetin binding to 0.4% HSA was reduced in accordance with the law of mass action and at Ct = 26.2 microgram/ml, 10.5% was free. Analysis of the 0.4% HSA data showed Tolmetin had 3 classes of binding sites (n1 = 1, K1 = 8.3 X 10(5) M-1; n2 = 4, K2 = 2.4 X 10(4) M-1; n3 = 44, K1 = 7.9 X 10(1) M-1). By studying the binding to 0.4% HSA at 23 degrees, it was established that the free energy change in binding for the first two classes of sites was entirely entropic in nature. Albumin accounted for almost all the binding of Tolmetin in human plasma. The effect of other drugs, the Tolmetin metabolite McN 2987 (5-p-carboxybenzoyl-1-methylpyrrole-2-acetic acid), tryptophan, and oleic acid on Tolmetin binding to 4% HSA was studied using ultrafiltration and 14C-tolmetin. Aspirin and salicyclic acid decreased Tolmetin binding and a combination of aspirin and salicyclic acid exerted a synergistic displacing effect. Indomethacin and ibuprofen had no effect while phenylhbutazone and acetaminophen increased Tolmetin binding slightly. Tolmetin binding was decreased slightly by McN 2987 and tryptophan and markedly increased by oleic acid. McN 2987 was not bound as extensively as Tolmetin. Binding of 14C-tolmetin to the plasma of 4 arthritic patients was studied by ultrafiltration and found to be less than to normal plasma and 4% HSA. Distribution of Tolmetin in the whole blood of 8 healthy subjects using a centrifugation technique showed that the drug was not taken up by red blood cells at therapeutic concentrations.
Disposition and irreversible plasma protein binding of Tolmetin in humans
Clin Pharmacol Ther 1988 Jul;44(1):107-14.PMID:3390998DOI:10.1038/clpt.1988.120.
The pharmacokinetics and irreversible plasma protein binding of Tolmetin were studied in six healthy subjects after the administration of a single, 400 mg dose of Tolmetin. With HPLC analysis, Tolmetin, Tolmetin glucuronide, and the isomers of Tolmetin glucuronide, which result from intramolecular acyl migration in vivo, were detected in the plasma up to 4 hours after administration, whereas these conjugates were present in the urine up to 24 hours. Irreversible binding of Tolmetin to plasma proteins occurred in all subjects. Irreversible binding exhibited a better correlation with exposure to Tolmetin glucuronide (r = 0.5618) and the isomers of Tolmetin glucuronide (r = 0.8200) than with exposure to Tolmetin (-0.3635). This is consistent with the hypothesis that covalent binding occurs via the acyl glucuronide.
Tolmetin sodium, a new anti-arthritis drug: double-blind and long-term studies
J Am Geriatr Soc 1976 Oct;24(10):440-6.PMID:61224DOI:10.1111/j.1532-5415.1976.tb03256.x.
The effectiveness of Tolmetin sodium in the treatment of rheumatoid arthritis was evaluated by: 1) a 12-week, double-blind study with a dosage range of 800-1600 mg daily; and 2) an open 2-year study with a dosage range of 400-2400 mg daily. The double-blind study involved 14 patients (7 Tolmetin sodium, 7 placebo), and the long-term study involved 24 patients. At frequent intervals, evaluations were made of joint pain, swelling, stiffness and inflammation; grip strength; walking time; and subjective well-being. Various laboratory tests were also performed. In the double-blind study, Tolmetin sodium proved superior to placebo and produced moderate improvement. In the long-term study, 5 patients improved markedly, 14 moderately, and 3 minimally. Severe side effefts were notably absent. Some mild side effects occurred but they were transient and did not interfere with therapy. Tolmetin sodium seems effective and safe in the management of rheumatoid arthritis.
Long-term therapy with Tolmetin in rheumatoid arthritis
J Clin Pharmacol 1983 Jul;23(7):287-300.PMID:6886030DOI:10.1002/j.1552-4604.1983.tb02739.x.
Data from over 1000 patients with rheumatoid arthritis who received Tolmetin sodium in double-blind and open studies have been pooled to assess long-term efficacy and safety. Duration of the studies was 12 weeks to 48 months. Mean age of patients was 54 years; ratio of males to females was 1:3. The results showed that Tolmetin provided rapid onset of action and continuous progressive decrease in symptoms in all measurements of inflammation. Mean number of painful joints was reduced from 22 at baseline to 16 at one month, to 9 at one year, and to 6 at two years. Duration of morning stiffness was 155 minutes at baseline, 123 minutes at one month, 74 minutes at one year, and 78 minutes at two years. The final global evaluation by the investigators showed that 61 per cent of patients had a marked or moderate response. Mean erythrocyte sedimentation rates did not increase during therapy with Tolmetin. Initial dose of Tolmetin in the patients pooled for this analysis was generally 600 to 800 mg/day, and the mean dose throughout the study was 1256 mg/day. The drug was well tolerated overall. As anticipated, gastrointestinal symptoms were the most frequently reported; nausea was experienced by 13 per cent of the patients at some time during therapy, and gastrointestinal distress, dyspepsia, or abdominal pain was reported by approximately 8.6 per cent each. Only 12.7 per cent of patients discontinued Tolmetin because of untoward reactions; 15.9 per cent of patients discontinued because of insufficient therapeutic response. The results of these long-term studies of patients with rheumatoid arthritis demonstrated that Tolmetin is an effective antiinflammatory agent with an acceptable record of safety.