ChemicalBook
Chinese Japanese Germany

Ketoconazole

Antifungal drug Pharmacological effects Pharmacokinetics Indications Side effects Precautions Pregnant and lactating women Chemical Properties Uses Production method Category Toxicity grading Acute toxicity Flammability and hazardous characteristics Storage characteristics Extinguishing agent
Ketoconazole
Ketoconazole
CAS No.
65277-42-1
Chemical Name:
Ketoconazole
Synonyms
Nizral;nizoral;kw-1414;R-41400;Fitonal;ketoderm;fungoral;Brizoral;Onofin K;fungarest
CBNumber:
CB9146879
Molecular Formula:
C26H28Cl2N4O4
Formula Weight:
531.43
MOL File:
65277-42-1.mol

Ketoconazole Properties

Melting point:
146°C
Density 
1.4046 (rough estimate)
refractive index 
-10.5 ° (C=0.4, CHCl3)
Flash point:
9℃
storage temp. 
2-8°C
solubility 
methanol: soluble50mg/mL
pka
pKa 3.25/6.22(H2O,t =25,I=0.025) (Uncertain)
color 
white to light yellow
Water Solubility 
Soluble in DMSO, ethanol, chloroform, water, and methanol.
Merck 
14,5302
CAS DataBase Reference
65277-42-1(CAS DataBase Reference)
SAFETY
  • Risk and Safety Statements
  • Hazard and Precautionary Statements (GHS)
Hazard Codes  T,N,F
Risk Statements  25-36/37/38-23/24/25-50/53-48/22-60-39/23/24/25-11
Safety Statements  36-45-36/37/39-26-61-60-53-36/37-16-7
RIDADR  UN 2811 6.1/PG 3
WGK Germany  3
RTECS  TK7912300
HazardClass  6.1(b)
PackingGroup  III
Hazardous Substances Data 65277-42-1(Hazardous Substances Data)
Toxicity LD50 in mice, rats, guinea pigs, dogs (mg/kg): 44, 86, 28, 49 i.v.; 702, 227, 202, 780 orally (Heel)
Symbol(GHS):
Signal word: Danger
Hazard statements:
Code Hazard statements Hazard class Category Signal word Pictogram P-Codes
H225 Highly Flammable liquid and vapour Flammable liquids Category 2 Danger P210,P233, P240, P241, P242, P243,P280, P303+ P361+P353, P370+P378,P403+P235, P501
H301 Toxic if swalloed Acute toxicity,oral Category 3 Danger P264, P270, P301+P310, P321, P330,P405, P501
H311 Toxic in contact with skin Acute toxicity,dermal Category 3 Danger P280, P302+P352, P312, P322, P361,P363, P405, P501
H331 Toxic if inhaled Acute toxicity,inhalation Category 3 Danger P261, P271, P304+P340, P311, P321,P403+P233, P405, P501
H360 May damage fertility or the unborn child Reproductive toxicity Category 1A, 1B Danger
H370 Causes damage to organs Specific target organ toxicity, single exposure Category 1 Danger P260, P264, P270, P307+P311, P321,P405, P501
H373 May cause damage to organs through prolonged or repeated exposure Specific target organ toxicity, repeated exposure Category 2 Warning P260, P314, P501
H400 Very toxic to aquatic life Hazardous to the aquatic environment, acute hazard Category 1 Warning P273, P391, P501
H402 Harmful to aquatic life Hazardous to the aquatic environment, acute hazard Category 3
H410 Very toxic to aquatic life with long lasting effects Hazardous to the aquatic environment, long-term hazard Category 1 Warning P273, P391, P501
H412 Harmful to aquatic life with long lasting effects Hazardous to the aquatic environment, long-term hazard Category 3 P273, P501
Precautionary statements:
P201 Obtain special instructions before use.
P210 Keep away from heat/sparks/open flames/hot surfaces. — No smoking.
P260 Do not breathe dust/fume/gas/mist/vapours/spray.
P273 Avoid release to the environment.
P280 Wear protective gloves/protective clothing/eye protection/face protection.
P311 Call a POISON CENTER or doctor/physician.
P301+P310 IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P303+P361+P353 IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P308+P313 IF exposed or concerned: Get medical advice/attention.
P405 Store locked up.
P501 Dispose of contents/container to..…

Ketoconazole price More Price(18)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich 420600 Ketoconazole 65277-42-1 50mg $109 2018-11-20 Buy
Sigma-Aldrich 1356508 Ketoconazole United States Pharmacopeia (USP) Reference Standard 65277-42-1 200mg $348 2018-11-13 Buy
TCI Chemical K0045 Ketoconazole >98.0%(HPLC)(T) 65277-42-1 1g $62 2018-11-22 Buy
TCI Chemical K0045 Ketoconazole >98.0%(HPLC)(T) 65277-42-1 5g $216 2018-11-22 Buy
Alfa Aesar J63367 Ketoconazole, 98% 65277-42-1 5g $170 2018-11-13 Buy

Ketoconazole Chemical Properties,Uses,Production

Antifungal drug

Ketoconazole is a broad-spectrum antifungal imidazole with commercially available product being under the trade name of Jindakening, Meikangling and keNing. It interferes with the activity of fungal cytochrome P-450 with a high selectivity, thus inhibiting the biosynthesis of ergosterol in fungal cell membrane. It is effective in treating both shallow, deep fungal infections and can inhibit both fungal growth and the transition from spores to mycelium to prevent the further infection. It has antifungal effect on Candida genus, Fonsecaea, Coccidioides, Histoplasma, Sporothrix spp and Trichophyton. Clinically, it is suitable for the treatment of ringworm, athlete's foot, and skin ringworm, tinea, jock itch, and thrush, tinea versicolor as well as cutaneous candidiasis.
Ketoconazole lotion, as a skin external use, is mainly used for clinical treatment and prevention of various kinds of infections caused by Malassezia such as tinea versicolor, seborrheic dermatitis and scalp pityriasis (dandruff), and can quickly alleviate the desquamation and itching caused by seborrheic dermatitis and scalp pityriasis.

Pharmacological effects

1. Pharmacology: ketoconazole belongs to azole-class antifungal drugs and has antifungal activity against various kinds of genus of deep fungal infections such as Candida, Fonsecaea, Coccidioides, Histoplasma, Sporothrix spp as well as Trichophyton. However, this product has a relative weak activity against Aspergillus, Sporothrix schenckii as well as some species of Dermateaceae and Mucor. This product, through actively interfering with the activity of cytochrome P-450, is capable of inhibiting the biosynthesis of the major steroids-ergosterol of the fungal cell membrane. Therefore, it destroys the fungal cell membrane and changes its permeability, resulting in the leakage of important intracellular material. Ketoconazole can also inhibit the biosynthesis of fungal triglyceride and phospholipid biosynthesis, inhibit the activity of oxidase and peroxidase, causing accumulation of intracellular hydrogen peroxide which further leads to cell submicroscopic structural degeneration and necrosis. For candida albicans, it can also suppress the transition process from spores to aggressive mycelium.
2. Toxicology: Long-term animal toxicity experiments have showed that ketoconazole can significantly increase the level of alkaline phosphatase and cause liver cell degeneration.

Pharmacokinetics

This product can be dissolved and absorbed in gastric acid. Upon the reduction of the acidity of gastric acid, its absorption can be reduced. Administration after meals can increase its absorption with the bioavailability of administration after meal being as high as 75%. After the single-dose oral administration of 200mg and 400mg, the peak plasma concentrations were 3.6 ± 1.65mg/L and 6.5 ± 1.44mg/L, respectively with the time for reaching peak being 1-4 hours. After the absorption, this product is widely distributed in the body and can reach the synovial fluid of inflammation, saliva, bile, urine, tendons, skin and soft tissue, feces and so on. It has a poor penetrating capability through the blood-brain barrier. In most cases, the drug concentration in the cerebrospinal fluid is less than 1mg/L. This product can also penetrate through the blood placental barrier. The binding rate of serum protein is about 90% or more with the elimination half-life being 6.5 to 9 hours. Some part of the drugs is subjected to metabolism in the liver through degradation into inactive imidazole ring and piperazine ring. The metabolites and prototype drug is mainly excreted through the bile. The drug excreted through the kidneys only accounts 13% of the administered dose, of which about 2% to 4% for drug prototype. The product can also be secreted into milk.

Indications

Ketoconazole is suitable for treating the following systemic fungal infections:
1. Candidiasis, chronic mucocutaneous candidiasis, oral candidiasis infection, Candida urinary tract infections as well as chronic, recurrent vaginal candidiasis which can be cured by topical therapy.
2. Dermatitis blastomycosis.
3. Coccidioidomycosis.
4. Histoplasmosis.
5. Chromomycosis.
6. Paracoccidioidomycosis.
It can be used for treating fungal skin diseases, hair ringworm and tinea versicolor caused by fungi and yeasts. When local therapy or oral administration of griseofulvin is invalid, or griseofulvin is unacceptable in the treatment of severe refractory fungal skin infection, we can choose the treatment of this drug.
The above information is edited by the chemicalbook of Dai Xiongfeng.

Side effects

External administration
1. Common erythema, burning, itching, stinging or other irritation, folliculitis, skin atrophy and thinning as well as telangiectasia.
2. It can be observed of dry skin, hirsutism, striae atrophicae and increased susceptibility to infection.
3. Long-term medication may cause cortex hyperthyroidism, manifested as hirsutism, acne, moon face, osteoporosis and other symptoms.
4. It can be occasionally observed of allergic contact dermatitis.
Side effects of oral administration
1. Hepatotoxicity: ketoconazole can cause increased serum aminotransferase (AST, ALT) level and is reversible. It can be occasionally observed of severe liver toxicity, primarily being liver cell type with the incidence being about 0.01%. The clinical manifestations include jaundice, dark urine, white-color faeces and abnormal fatigue, etc., these effects can usually resume after the withdrawal of the drug, but there are also cases of deaths; there are also cases of hepatitis in children.
2. Gastrointestinal reaction: nausea, vomiting and anorexia are common cases.
3. Gynecomastia and lack of semen; this is related to the effect of this product on suppression of the biosynthesis of testosterone and adrenal cortical hormone.

Precautions

1. Take it with caution upon the following cases:
lack of gastric acid (may cause the reduction of the absorption of the product).
Alcoholism or liver damage (it can cause liver toxicity).
2.Before or during the treatment, the patients should be regularly subject to monitoring of liver function. Elevated serum aminotransferase may not be accompanied by symptoms of hepatitis, however, if the serum aminotransferase value continues to rise or increase, or associated with liver toxicity symptoms, we should discontinue ketoconazole treatment.
3. For simultaneous administration of cimetidine or furan thiamine, take them at least 2 hours after taking this drug.
4. This product can cause photosensitivity reactions. Therefore, during the medication, we should avoid prolonged exposure to bright light and can wear colored glasses. 5. It is not allowed to take alcoholic beverages while taking the drug. Pay attention if dizziness or drowsiness occurs.
5. Patients of renal dysfunction don’t need to be subject to reduced dose upon taking it.
6. Ketoconazole has a very poor capability of penetrating blood-brain barrier and is not suitable for the treatment of fungal meningitis. This product also has poor efficacy in treating Aspergillus, Mucor or maduromycosis and thus is also not suitable.
7. Interfere with the diagnosis: can cause elevated serum aminotransferase, can also cause increased level of hemobilirubin.

Pregnant and lactating women

The product can penetrate through the blood placental barrier. Animal experiments have shown that the product can be teratogenic such as syndactylia, lack of finger (toe) and dystocia in rats. US FDA data has shown that the application of this drug in pregnant women should be classified into Class C, namely being toxic in animal studies but is lack of adequate information in human studies. Therefore, pregnant women should be avoided for using it. Ketoconazole can be secreted into breast milk. The administration of it for humans has not found any issues, but the product can increase the likelihood of the occurrence of neonatal kernicterus, lactating women should weigh both advantages and disadvantages for using it.

Chemical Properties

It is white crystalline powder with the melting point being 146 ℃ and insoluble in water.

Uses

It is antifungal drug for being used to treat athlete's foot and excessive dandruff.

Production method

Put the mixture containing 2.4 parts of 1-acetyl-4-(4-hydroxyphenyl) piperazine, 0.4 part of 78% sodium hydride, 75 parts of dimethyl sulfate, 22.5 parts of benzene at 40 ℃ for stirring of 1 hour, followed by addition of 4.2 parts of 2-(2,4-dichlorobenzyl-2-(1H-imidazol-1-yl-methyl)-1,3-dioxolane-4-ylmethyl methanesulfonate. Stir at 100 °C overnight with the reaction product resulting in 3.2 parts ketoconazole after treatment.

Category

Toxic substances

Toxicity grading

Highly toxic

Acute toxicity

Oral-rat LD50: 166 mg/kg; Oral-Mouse LD50: 618 mg/kg.

Flammability and hazardous characteristics

It is combustible with burning releasing toxic chloride fumes and nitrogen oxides.

Chemical Properties

White or almost white powder.

Storage characteristics

Treasury: ventilation, low-temperature and dry; store it separately from food raw materials.

Uses

Inhibits cytochrome P-450 dependent steps in the biosynthesis of steroid hormones in vivo. Antimetastatic and antineoplastic activity. Orally active 5-lipoxygenase and thromboxane synthase inhibitor

Uses

antifungal, PXR/SRC1 & CAR/SRC1 inhibitor

Uses

For the treatment of the following systemic fungal infections: candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis.

Uses

An inhibitor of CYP proteins, thromboxane synthetase, and 5-LO

brand name

Ketozole (Taro); Nizoral (Janssen); Nizoral (McNeil).

Extinguishing agent

Dry powder, foam, sand, carbon dioxide, water mist.

Biological Activity

Antifungal agent; potent inhibitor of cytochrome P450c17.

Ketoconazole Preparation Products And Raw materials

Raw materials

Preparation Products


Ketoconazole Suppliers

Global( 387)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Shenzhen Sendi Biotechnology Co.Ltd.
0755-23311925 18102838259
0755-23311925 Abel@chembj.com CHINA 3218 55
Henan DaKen Chemical CO.,LTD.
+86-371-55531817
info@dakenchem.com CHINA 22063 58
Nanjing Gold Pharmaceutical Technology Co. Ltd.
025-84209270 15906146951
025-84209270 wgp@nanjing-pharmaceutical.com CHINA 117 55
Hebei Jiangkai Trading Co., Ltd
0086-17197824289/17197824028
alice@hbjkai.com CHINA 277 58
Shanghai Bojing Chemical Co.,Ltd.
+86-21-37122233
+86-21-37127788 Candy@bj-chem.com CHINA 500 55
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com CHINA 20795 55
Mainchem Co., Ltd.
+86-0592-6210733
+86-0592-6210733 sales@mainchem.com CHINA 32764 55
PI & PI BIOTECH INC.
020-81716320
020-81716319 Sales@pipitech.com CHINA 2549 55
Hubei XinRunde Chemical Co., Ltd.
+8615102730682; +8618874586545
02783214688 bruce@xrdchem.cn CHINA 551 55
Hefei TNJ Chemical Industry Co.,Ltd.
86-0551-65418684 18949823763
86-0551-65418684 info@tnjchem.com China 1582 55

View Lastest Price from Ketoconazole manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2018-03-15 Ketoconazole
65277-42-1
US $10.00 / KG 10G 99% 10MT Hubei XinRunde Chemical Co., Ltd.
2018-12-17 Ketoconazole
65277-42-1
US $7.00 / kg 1kg 99% 100KG career henan chemical co
2018-12-17 Ketoconazole
65277-42-1
US $1.00 / kg 1kg 99% Customized career henan chemical co

65277-42-1(Ketoconazole)Related Search:


Copyright 2017 © ChemicalBook. All rights reserved