4-hydroxy Tolbutamide
(Synonyms: 4-羟基甲苯磺丁脲,Hydroxytolbutamide) 目录号 : GC42414A CYP2C8 and CYP2C9 metabolite of tolbutamide
Cas No.:5719-85-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
4-hydroxy Tolbutamide is a cytochrome P450 2C8 (CYP2C8) and CYP2C9 metabolite of tolbutamide, a first-generation potassium channel blocker. Tolbutamide 4-hydroxylation is an often used probe reaction in the pharmaceutical industry for the characterization of CYP2C8 and CYP2C9 involvement in the metabolism of clinical drugs.
| Cas No. | 5719-85-7 | SDF | |
| 别名 | 4-羟基甲苯磺丁脲,Hydroxytolbutamide | ||
| Canonical SMILES | CCCCNC(=O)NS(=O)(=O)c1ccc(CO)cc1 | ||
| 分子式 | C12H18N2O4S | 分子量 | 286.4 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| 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 | 3.4916 mL | 17.4581 mL | 34.9162 mL |
| 5 mM | 0.6983 mL | 3.4916 mL | 6.9832 mL |
| 10 mM | 0.3492 mL | 1.7458 mL | 3.4916 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。
Pharmacokinetics of tolbutamide and its metabolite 4-hydroxy Tolbutamide in poloxamer 407-induced hyperlipidemic rats
Biopharm Drug Dispos 2014 Jul;35(5):264-74.PMID:24590592DOI:10.1002/bdd.1893.
Under hyperlipidemic conditions, there are likely to be alterations in the pharmacokinetics of CYP2C11 substrates following decreased expression of CYP2C11, which is homologous to human CYP2C9. The pharmacokinetics of tolbutamide (TB) and its metabolite 4-hydroxy Tolbutamide (4-OHTB) were evaluated as a CYP2C11 probe after intravenous and oral administration of 10 mg/kg tolbutamide to poloxamer 407-induced hyperlipidemic rats (HL rats). Changes in the expression and metabolic activity of hepatic CYP2C11 and the plasma protein binding of tolbutamide in HL rats were also evaluated. The total area under the plasma concentration-time curve (AUC) of tolbutamide in HL rats after intravenous administration was comparable to that in controls due to their comparable non-renal clearance (CLNR ). The free fractions of tolbutamide in plasma were comparable between the control and HL rats. The 4-hydroxylated metabolite formation ratio (AUC4-OHTB /AUCTB ) in HL rats was significantly smaller than that in the control rats as a result of the reduced expression of hepatic CYP2C11 (by 15.0%) and decreased hepatic CLint (by 28.8%) for metabolism of tolbutamide to 4-OHTB via CYP2C11. Similar pharmacokinetic changes were observed in HL rats after oral administration of tolbutamide. These findings have potential therapeutic implications, assuming that the HL rat model qualitatively reflects similar changes in patients with hyperlipidemia. Since other sulfonylureas in clinical use are substrates of CYP2C9, their hepatic CLint changes have the potential to cause clinically relevant pharmacokinetic changes in a hyperlipidemic state.
Effect of albumin on phenytoin and tolbutamide metabolism in human liver microsomes: an impact more than protein binding
Drug Metab Dispos 2002 Jun;30(6):648-54.PMID:12019190DOI:10.1124/dmd.30.6.648.
The cytochrome P450 (P450)-dependent conversion of phenytoin (PHT) to p-hydroxy phenytoin (pHPPH), and tolbutamide (TLB) to 4-hydroxy Tolbutamide (hydroxy-TLB), in human liver microsomes was studied in the presence of increasing concentrations (0-4%) of bovine serum albumin (BSA). Therefore, the free fraction (f(u)) of PHT and TLB varied. Whereas the f(u) of PHT (5 microM) decreased, an increase (3-fold), rather than a decrease in the pHPPH formation rate was observed when BSA (<1%) was present. The stimulation was attributed to a significant decrease in apparent K(m). The change, however, was diminished as the BSA concentration reached 4% (PHT f(u) = 0.2), in which the reaction velocity remained the same as that measured in the absence of BSA. Therefore, unchanged K(m) (16.2 +/- 0.7 microM) and V(max) (9.4 +/- 0.2 pmol/min/mg of protein) values were determined based on total PHT concentrations, whereas correction for f(u) led to an unbound K(m) (K(mu)) of approximately 3.2 microM. Similarly, the metabolism of TLB (50 microM) was enhanced (approximately 2-fold) in the presence of 0.25% BSA but remained only 35% of the control activity (no BSA) at 1% BSA. However, the remaining activity was higher (3-fold) than that determined with an equivalent free concentration of TLB (4 microM) calculated according to its f(u) (0.08). The difference became less significant when BSA concentration was 4% (f(u) < 0.02). Collectively, the results suggest a 2-fold effect of BSA on PHT and TLB hydroxylation: first, facilitation of the reactions via a decrease in K(m); second, a decrease in f(u) leading to a drop in reaction rate. For a given P450 reaction, therefore, the effect of BSA may depend upon enzyme affinity, catalytic capacity, and the extent of protein binding.
In vitro interaction of the antipsychotic agent olanzapine with human cytochromes P450 CYP2C9, CYP2C19, CYP2D6 and CYP3A
Br J Clin Pharmacol 1996 Mar;41(3):181-6.PMID:8866916DOI:10.1111/j.1365-2125.1996.tb00180.x.
1. The ability of olanzapine to inhibit the metabolism of marker catalytic activities for the cytochromes P450 CYP3A, CYP2D6, CYP2C9, and CYP2C19 was examined. This inhibitory capability was compared with that obtained with clozapine and known inhibitory compounds for the same cytochromes P450. 2. Olanzapine, clozapine, and ketoconazole were all found to non-competitively inhibit 1'-hydroxy midazolam formation, form selective for CYP3A, yielding Ki values of 491, 99 and 0.11 microM, respectively. The 1'-hydroxylation of bufuralol, form selective for CYP2D6, was competitively inhibited by olanzapine (Ki = 89 microM), clozapine (Ki = 19 microM), and quinidine (Ki = 0.03 microM). Tolbutamide metabolism to 4-hydroxy Tolbutamide, form selective for CYP2C9, was competitively inhibited by clozapine and phenytoin (Ki of 31 microM and 17 microM, respectively). Olanzapine non-competitively inhibited tolbutamide metabolism with a Ki of 715 microM. The marker catalytic activity for CYP2C19 mediated metabolism, 4'-hydroxy S-mephenytoin formation, was competitively inhibited by clozapine (Ki = 69 microM) and omeprazole (Ki = 4.1 microM). Non-competitive inhibition of CYP2C19 mediated metabolism was seen with olanzapine with a Ki of 920 microM. 3. The calculated percent inhibition by olanzapine of substrates metabolized by CYP3A, CYP2D6, CYP2C9, and CYP2C19 was modeled assuming a total plasma concentration in the therapeutic range (0.2 microM). Total olanzapine vs unbound olanzapine was used to model the worst case (most conservative) situation. In all cases, the calculated percent inhibition of these cytochromes P450 by olanzapine was < 0.3%, suggesting that there would be little in vivo inhibition of the metabolism of substrates of these enzymes when co-administered with olanzapine.