体外活性：灰黄霉素对小孢子菌属、毛癣菌属和表皮癣菌属等不同种类的皮肤癣菌具有活性。其他真菌如短柄帚霉（Scopulariopsis brevicaulis）和圆环酵母（Hendersomula toruloidea）则不敏感。灰黄霉素对酵母和细菌几乎没有作用或没有作用。体外测试的灰黄霉素对各种皮肤癣菌的最低抑制浓度范围在 0.14 至 0.6 μg/mL 之间。灰黄霉素对细胞有丝分裂的主要影响是纺锤体微管的瓦解。灰黄霉素还能够诱导哺乳动物细胞染色体结构畸变。灰黄霉素抑制人结肠腺癌细胞 COLO 205 和 HT 29、肝癌细胞 Hep G2 和 Hep 3B、白血病细胞 HL 60 和正常角质形成细胞 (#76 KhGH) 的活力，IC50 分别为 ~1 和 ~5 μM、5 和 5 μM 、 1 μM 和 50 μM，分别在 30 小时孵育后。灰黄霉素 (20 μM) 会在 HT 29 细胞中诱导明显存在的异常有丝分裂纺锤体形成（具有不同长度的单极、双极和三极纺锤体），并通过细胞周期蛋白 B1/cdc2 激酶升高导致 24 小时 G2/M 细胞周期停滞myt-1 蛋白表达的活性和下调。 Griseofulvin 能够通过 caspase3 激活、Bcl-2 过度磷酸化以及抑制与 Bax 相关的 Bcl-2 正常功能来诱导 HT 29 细胞凋亡。细胞测定：在存在或不存在指定浓度的灰黄霉素的情况下，将细胞 (5×103/mL) 在 96 孔板中一式三份孵育，最终体积为 0.2 mL，在 37 ℃ 下孵育不同的时间间隔。此后，将 20 μL MTT 溶液（PBS 中 5 mg/mL）添加到每个孔中。 37 ℃孵育2小时后，加入0.1 mL裂解缓冲液（20% SDS、50%二甲基甲酰胺），37 ℃继续孵育过夜，然后用酶标仪测量570 nm处的光密度。

灰黄霉素在体内表现出有效的抗感染活性。灰黄霉素每日经口给予的最低有效剂量，对于患有五毛癣菌皮肤感染的小鼠为 250 mg/kg（6 天），对于患有须毛癣菌皮肤感染的豚鼠为 25 mg/kg（12 天）。灰黄霉素 (50 mg/kg) 能够抑制 COLO 205 肿瘤异种移植物的生长。灰黄霉素和诺考达唑 (5 mg/kg) 一起治疗可显着增强诺考达唑的疗效，导致肿瘤生长停止。

Absorption, Distribution and Excretion
Poorly absorbed from GI ranging from 25 to 70% of an oral dose. Absorption is significantly enhanced by administration with or after a fatty meal.
IN RATS GIVEN ORAL DOSES OF 100 MG/KG BODY WT (36)CL-GRISEOFULVIN, 10% OF ACTIVITY WAS FOUND IN URINE AFTER 24 HR & 4% DURING 24-48 HR. ...IN ANOTHER STUDY, WITHIN 24-HR PERIOD ONLY 0.14% OF SIMILAR ORAL DOSES IN RATS WAS FOUND IN URINE, & 16% WAS RECOVERED IN FECES. FOLLOWING ITS IV INJECTION GRISEOFULVIN WAS DISTRIBUTED EVENLY THROUGHOUT TISSUES, ALTHOUGH HIGHER LEVELS WERE FOUND IN SKIN & LUNG.
Microsize - variable, ranging from 25 to 70% of an oral dose. Ultramicrosize - Almost completely absorbed. Absorption is significantly enhanced by administration with or after a fatty meal.
Griseofulvin is deposited in varying concentrations in the keratin layer of the skin, hair, and nails. It can be detected in the stratum corneum of the skin within a few hours following administration. Only a very small fraction of an oral dose is distributed in the body fluids and tissues.
Elimination: Renal. less than 1% of a dose is excreted as unchanged drug in the urine. Approximately 36% of griseofulvin is excreted unchanged in the feces.
GRISEOFULVIN IS PROBABLY DEPOSITED IN BASAL CELLS AND IS CARRIED OUTWARDS INTO EPIDERMIS AS NORMAL SKIN GROWTH PROCEEDS. THIS...MAKES FOR LONG LATENCY FROM TIME MEDICATION IS BEGUN UNTIL EVIDENCE OF IMPROVEMENT OCCURS.

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Metabolism / Metabolites
Primarily hepatic with major metabolites being 6-methyl-griseofulvin and its glucuronide conjugate.
Griseofulvin is mainly metabolized to 6-dimethylgriseofulvin and its glucuronide.
...IT HAS BEEN REPORTED THAT 6-DEMETHYLGRISEOFULVIN IS THE MAJOR URINARY METABOLITE...IN MAN, THE PREVIOUSLY REPORTED 4-DEMETHYL-GRISEOFULVIN WAS ABSENT. GRISEOFULVIC ACID (7-CHLORO-4,6-DIMETHOXY-6'-METHYLGRISAN-2',3,4'-TRIONE) WAS IDENTIFIED...
Primarily hepatic with major metabolites being 6-methyl-griseofulvin and its glucuronide conjugate.
Half Life: 9-21 hours

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Biological Half-Life
9-21 hours
DRUG HAS A HALF-LIFE IN PLASMA OF ABOUT 1 DAY, & APPROX 50% OF ORAL DOSE CAN BE DETECTED IN THE URINE WITHIN 5 DAYS, MOSTLY IN THE FORM OF METABOLITES /SRP: 36% IN THE FECES WITHIN 5 DAYS/.
The half-life of griseofulvin in canine plasma was found to be 47 minutes ... .

Toxicity Summary
Griseofulvin is fungistatic, however the exact mechanism by which it inhibits the growth of dermatophytes is not clear. It is thought to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin. It binds to keratin in human cells, then once it reaches the fungal site of action, it binds to fungal microtubes thus altering the fungal process of mitosis.

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Hepatotoxicity
Transient mild-to-moderate elevations in serum aminotransferase levels occur in up to 5% of patients treated with griseofulvin, but these abnormalities are usually asymptomatic and resolve even with continuation of the medication. Clinically apparent hepatotoxicity is rare and only isolated case reports have been published. The liver injury is typically cholestatic and usually arises within the first few months of therapy. Signs of hypersensitivity such as fever, rash and eosinophilia are rare but griseofulvin can include hypersensitivity reactions and at least one case of DRESS syndrome accompanied by serum aminotransferase elevations has been reported with its use. Published cases of griseofulvin induced liver injury have all been self-limited, recovery requiring 1 to 3 months. Griseofulvin can increase intrahepatic levels of protoporphyrin and induce acute attacks of porphyria in patients with acute intermittent porphyria in remission.
Likelihood score: C (probable rare cause of clinically apparent liver injury).

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Interactions
...METABOLISM /OF GRISEOFULVIN/ IS ACCELERATED BY...PRIMIDONE IN RATS AND MAN...
GRISEOFULVIN ACTED AS A COCARCINOGEN WITH SKIN APPLICATIONS OF 3-METHYLCHOLANTHRENE IN MICE...
Effects may be potentiated when alcohol is used concurrently with griseofulvin; also, concurrent use with griseofulvin may result in tachycardia, diaphoresis, and flushing.
/Coumarin- or indandione-derivative anticoagulants/ effects, may be decreased when these agents are used concurrently with griseofulvin; decrease is thought to be due to accelerated metabolism of anticoagulants secondary to stimulation of hepatic microsomal enzyme activity; prothrombin time should be monitored until a stable level is maintained; dosage adjustments may be necessary during and after griseofulvin therapy.
For more Interactions (Complete) data for GRISEOFULVIN (6 total), please visit the HSDB record page.

Mutat Res.1988 Mar;195(2):91-126;Int J Cancer.2001 Feb 1;91(3):393-401.

Griseofulvin can cause cancer according to The World Health Organization's International Agency for Research on Cancer (IARC).
Griseofulvin appears as white to pale cream-colored crystalline powder. Odorless or almost odorless. Tasteless. Sublimes without decomposition at 410 °F. (NTP, 1992)
Griseofulvin is an oxaspiro compound produced by Penicillium griseofulvum. It is used by mouth as an antifungal drug for infections involving the scalp, hair, nails and skin that do not respond to topical treatment. It has a role as an antibacterial agent and a Penicillium metabolite. It is an organochlorine compound, a member of 1-benzofurans, an oxaspiro compound, an antibiotic antifungal drug and a benzofuran antifungal drug.
An antifungal antibiotic. Griseofulvin may be given by mouth in the treatment of tinea infections.
Griseofulvin is a Tubulin Inhibiting Agent. The physiologic effect of griseofulvin is by means of Decreased Mitosis, and Microtubule Inhibition.
Griseofulvin is a Tubulin Inhibiting Agent. The physiologic effect of griseofulvin is by means of Decreased Mitosis, and Microtubule Inhibition.
Griseofulvin is a fungistatic agent used to treat superficial fungal skin infections such as tinea capitis and pedis. Griseofulvin therapy can cause transient mild-to-moderate serum aminotransferase elevations and has very rarely been linked to clinically apparent acute drug induced liver injury.
Griseofulvin has been reported in Penicillium aethiopicum, Penicillium canescens, and other organisms with data available.
Griseofulvin is an antifungal agent derived from the mold Penicillium griseofulvum that is used to treat fungal infections of the skin and nails. Griseofulvin binds to tubulin, disrupting microtubule function and inhibiting mitosis.
Griseofulvin is only found in individuals that have used or taken this drug. It is an antifungal antibiotic. Griseofulvin may be given by mouth in the treatment of tinea infections. Griseofulvin is fungistatic, however the exact mechanism by which it inhibits the growth of dermatophytes is not clear. It is thought to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin. It binds to keratin in human cells, then once it reaches the fungal site of action, it binds to fungal microtubes thus altering the fungal process of mitosis.
An antifungal agent used in the treatment of TINEA infections.
See also: Griseofulvin, ultramicrocrystalline (has subclass); Griseofulvin, microcrystalline (has subclass); Griseofulvin, ultramicrosize (annotation moved to).

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Drug Indication
For the treatment of ringworm infections of the skin, hair, and nails, namely: tinea corporis, tinea pedis, tinea cruris, tinea barbae, cradle cap or other conditions caused by Trichophyton or Microsporum fungi.
FDA Label

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Mechanism of Action
Griseofulvin is fungistatic, however the exact mechanism by which it inhibits the growth of dermatophytes is not clear. It is thought to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin. It binds to keratin in human cells, then once it reaches the fungal site of action, it binds to fungal microtubes thus altering the fungal process of mitosis.
Fungistatic; griseofulvin inhibits fungal cell mitosis by causing disruption of the mitotic spindle structure, thereby arresting the metaphase of cell division. It is deposited in varying concentrations in the keratin precursor cells of skin, hair, and nails, rendering the keratin resistant to fungal invasion. As the infected keratin is shed, it is replaced with healthy tissue.

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Therapeutic Uses
Antibiotics, Antifungal
GRISEOFULVIN IS USED IN THE TREATMENT OF TINEAS (RINGWORM INFECTIONS) OF THE SKIN, HAIR & NAILS--TINEA CORPORIS, TINEA PEDIS, TINEA CRURIS, TINEA BARBAE, TINEA CAPITIS & TINEA UNGUIUM (ONYCHOMYCOSIS) CAUSED BY SUSCEPTIBLE SPECIES OF TRICHOPHYTON, MICROSPORUM, OR EPIDERMOPHYTON.
MEDICATION (VET): DRUG IS USEFUL IN TREATMENT OF SUPERFICIAL FUNGUS INFECTIONS CAUSED BY TRICHOPHYTON MENTAGROPHYTES, RUBRUM, INTERDIGITALE, SCHOENLEINI, SULPHUREUM AND VERRUCOSUM, AND MICROSPORUM AND OVINI, CANIS, AND GYPSEUM...
MEDICATION (VET): TO TREAT RINGWORM OF SKIN OR NAILS ESPECIALLY THOSE AREAS DIFFICULT TO TREAT LOCALLY (EYE, MOUTH, NAIL AREAS), OR THOSE REFRACTORY TO OTHER THERAPY.
For more Therapeutic Uses (Complete) data for GRISEOFULVIN (14 total), please visit the HSDB record page.

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Drug Warnings
ORAL THRUSH DUE TO CANDIDAL OVERGROWTH HAS...OCCURRED.
GRISEOFULVIN...IS CONTRAINDICATED IN PATIENTS WITH ACUTE INTERMITTENT PORPHYRIA OR A HISTORY OF.../IT/, HEPATOCELLULAR FAILURE, AND HYPERSENSITIVITY TO THE DRUG. ... SAFE USE...DURING PREGNANCY HAS NOT BEEN ESTABLISHED.
RARELY, TRANSIENT DIMINUTION OF HEARING HAS OCCURRED...PARESTHESIAS OF HANDS AND FEET HAS FOLLOWED EXTENDED THERAPY... OCCASIONALLY, LARGE DOSES HAVE PRODUCED...PSYCHOTIC SYMPTOMS.
GRISEOFULVIN HAS BEEN REPORTED TO CAUSE TACHYCARDIA AND FLUSHING...
For more Drug Warnings (Complete) data for GRISEOFULVIN (17 total), please visit the HSDB record page.

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Pharmacodynamics
Griseofulvin is a mycotoxic metabolic product of Penicillium spp. It was the first available oral agent for the treatment of dermatophytoses and has now been used for more than forty years. Griseofulvin is fungistatic with in vitro activity against various species of Microsporum Epidermophyton, and Trichophyton. It has no effect on bacteria or on other genera of fungi. Following oral administration, griseofulvin is deposited in the keratin precursor cells and has a greater affinity for diseased tissue. The drug is tightly bound to the new keratin which becomes highly resistant to fungal invasions. Once the keratin-Griseofulvin complex reaches the skin site of action, it binds to fungal microtubules (tubulin) thus altering fungal mitosis.

C17H17CLO6

352.77

352.071

126-07-8

Griseofulvin;126-07-8

441140

White to off-white solid powder

1.4±0.1 g/cm3

570.4±50.0 °C at 760 mmHg

218-220 °C(lit.)

228.0±29.1 °C

0.0±1.6 mmHg at 25°C

1.583

3.53

71.06

0

6

3

24

575

2

C[C@@H]1CC(=O)C=C([C@]12C(=O)C3=C(O2)C(=C(C=C3OC)OC)Cl)OC

DDUHZTYCFQRHIY-RBHXEPJQSA-N

InChI=1S/C17H17ClO6/c1-8-5-9(19)6-12(23-4)17(8)16(20)13-10(21-2)7-11(22-3)14(18)15(13)24-17/h6-8H,5H2,1-4H3/t8-,17+/m1/s1

(2S,6R)-7-chloro-2,4,6-trimethoxy-6-methyl-3H-spiro[benzofuran-2,1-cyclohexan]-2-ene-3,4-dione

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)

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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。