Stiripentol (STP) 是一种抗惊厥药物，可以阻断 CYP3A4（非竞争性）和 CYP2C19（竞争性）CLB 的 N-去甲基化为 N-去甲基氯巴扎姆 (NCLB)。解释Stiripentol (STP)抑制CLB去甲基化的最佳模型是表达cDNA的CYP2C19的竞争性抑制模型（Ki=0.52 μM）和表达cDNA的CYP3A4的表观Ki=1.6 μM的非竞争性抑制模型。 Stiripentol (STP) 的 Ki=0.14 μM，通过表达 CYP2C19 的 cDNA 竞争性抑制 NCLB 形成 OH-NCLB [1]。

接受司替戊醇（STP）单药治疗的小鼠中，BT1（39.67±1.09°C）和BT2（41.32±1.05°C）之间的温度差异达到统计学显着性（t=3.097，p<0.05）。司替戊醇 (STP) 单药治疗与 CLB 单药治疗之间，BT2 存在统计学显着性差异 (t=2.615，p<0.05)。接受司替戊醇（STP）+CLB联合治疗的小鼠BT1（40.18±0.58℃）和BT2（43.03±0.49℃）之间的差异达到统计学意义（t=10.44，p<0.01）[2]。

Absorption, Distribution and Excretion
After oral administration, stiripentol is quickly and readily absorbed with a median Tmax of two to three hours. The systemic exposure increases dose-proportionally. Stiripentol has a low bioavailability due to water insolubility and extensive metabolism.
Stiripentol is mainly eliminated via metabolism. Its metabolites are excreted mainly via the kidney. Urinary metabolites of stiripentol accounted collectively for the majority (73%) of an oral acute dose whereas a further 13-24% was recovered in feces as unchanged drug.
The average volume of distribution is 1.03 L/kg but does not display a dose-dependent relationship. Following administration, stiripentol enters the brain and accumulates in the cerebellum and medulla.
Plasma clearance decreases markedly at high doses; it falls from approximately 40 L/kg/day at the dose of 600 mg/day to about 8 L/kg/day at the dose of 2,400 mg. Clearance is decreased after repeated administration of stiripentol, probably due to inhibition of the cytochrome P450 isoenzymes responsible for its metabolism.

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Metabolism / Metabolites
Stiripentol is extensively metabolized. About 13 different metabolites have been found in urine. The main metabolic processes are demethylenation (oxidative cleavage of the methylenedioxy ring system) and glucuronidation, although precise identification of the enzymes involved has not yet been achieved. Other metabolic pathways include O-methylation of catechol metabolites, hydroxylation of the t-butyl group, and conversion of the allylic alcohol side-chain to the isomeric 3-pentanone structure. _In vitro_ studies suggested that the phase I metabolism of stiripentol is catalyzed by CYP1A2, CYP2C19 and CYP3A4 and possibly other enzymes.

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Biological Half-Life
The elimination half life is approximately ranges from 4.5 to 13 hours, in a dose-dependent manner.

Hepatotoxicity
Limited data are available on the safety of stiripentol, based mainly on open-label and small, placebo controlled clinical trials in children with Dravet syndrome. In these studies, addition of stiripentol to chronic clobazam therapy was not associated with an increased frequency of serum aminotransferase elevations, and there were no instances of clinically apparent liver injury. Long term therapy with stiripentol has been linked to low rates of ALT and alkaline phosphatase elevations but with increases in gamma glutamyl transpeptidase (GGT) in up to 38% of cases. Since its general availability, there have been no published case reports of stiripentol hepatotoxicity. Thus, clinically apparent liver injury due to stiripentol must be rare, if it occurs at all.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because no information is available on the use of stiripentol during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Protein binding of stiripentol is 99%.

[1]. In vitro and in vivo inhibitory effect of stiripentol on clobazam metabolism.Drug Metab Dispos. 2006 Apr;34(4):608-11. Epub 2006 Jan 13.

[2]. Efficacy of stiripentol in hyperthermia-induced seizures in a mouse model of Dravet syndrome. Epilepsia. 2012 Jul;53(7):1140-5.

Pharmacodynamics
Stiripentol is an antiepileptic agent that works to reduce seizure frequency. It demonstrates anticonvulsant properties when administered alone and may potentiate GABAergic inhibition via several proposed mechanisms. It provides a therapeutic advantage in improving the efficacy of other antiepileptic drugs by inhibiting cytochrome P450 enzymes that normally metabolize those drugs. The anticonvulsant activity of stiripentol is age-dependent, with increased efficacy in younger patients.

C₁₄H₁₈O₃

234.29

234.125

49763-96-4

Stiripentol-d9;1185239-64-8

5311454

White to off-white solid powder

1.1±0.1 g/cm3

365.4±11.0 °C at 760 mmHg

73-74ºC

174.8±19.3 °C

0.0±0.9 mmHg at 25°C

1.579

3.39

38.69

1

3

3

17

280

0

CC(C)(C)C(/C=C/C1=CC2=C(C=C1)OCO2)O

IBLNKMRFIPWSOY-FNORWQNLSA-N

InChI=1S/C14H18O3/c1-14(2,3)13(15)7-5-10-4-6-11-12(8-10)17-9-16-11/h4-8,13,15H,9H2,1-3H3/b7-5+

(E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-ol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.08 mg/mL (8.88 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (8.88 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (8.88 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。