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药品详细

Clotrimazole(克霉唑)

化学结构式图
中文名
克霉唑
英文名
Clotrimazole
分子式
C22H17ClN2
化学名
1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole
分子量
Average: 344.837
Monoisotopic: 344.108026261
CAS号
23593-75-1
ATC分类
A01A 未知;D01A 未知;G01A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. [PubChem]

生产厂家
  • Actavis mid atlantic llc
  • Bayer healthcare pharmaceuticals inc
  • Bayer pharmaceuticals corp
  • Glenmark pharmaceuticals inc usa
  • Nycomed us inc
  • Paddock laboratories inc
  • Roxane laboratories inc
  • Schering corp sub schering plough corp
  • Schering plough healthcare products inc
  • Taro pharmaceuticals inc
  • Taro pharmaceuticals usa inc
  • Teva pharmaceuticals usa
  • Teva pharmaceuticals usa inc
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
规格
化合物类型
Type small molecule
Classes
  • Diphenylmethanes
Substructures
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Diphenylmethanes
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Cyanamides
适应症
药理
Indication For the local treatment of oropharyngeal candidiasis and vaginal yeast infections, also used in fungal infections of the skin such as ringworm, athlete's foot, and jock itch.
Pharmacodynamics Clotrimazole, an imidazole derivative with a broad spectrum of antimycotic activity, inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. Betamethasone and clotrimazole are used together to treat cutaneous tinea infections. In studies in fungal cultures, the minimum fungicidal concentration of clotrimazole caused leakage of intracellular phosphorous compounds into the ambient medium with concomitant breakdown of cellular nucleic acids, and accelerated potassium etflux. Both of these events began rapidly and extensively after addition of the drug to the cultures. The primary action of clotrimazole is against dividing and growing organisms.
Mechanism of action Clotrimazole interacts with yeast 14-α demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol, an essential component of the membrane. In this way, clotrimazole inhibits ergosterol synthesis, resulting in increased cellular permeability. Clotrimazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms and the uptake of purine, impair triglyceride and/or phospholipid biosynthesis, and inhibit the movement of calcium and potassium ions across the cell membrane by blocking the ion transport pathway known as the Gardos channel.
Absorption Poorly and erratically absorbed orally, minimal vaginal or topical absorption.
Volume of distribution Not Available
Protein binding 90%
Metabolism
Hepatic (metabolized to inactive metabolites)
Route of elimination Not Available
Half life 2 hours
Clearance Not Available
Toxicity Symptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps.
Affected organisms
  • Yeast and other fungi
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 148 °C PhysProp
water solubility 29.84 mg/mL Not Available
logP 6.1 Not Available
Predicted Properties
Property Value Source
water solubility 1.47e-03 g/l ALOGPS
logP 5.48 ALOGPS
logP 5.84 ChemAxon
logS -5.4 ALOGPS
pKa (strongest basic) 6.62 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 1 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 17.82 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 103.76 ChemAxon
polarizability 36.25 ChemAxon
药物相互作用
Drug Interaction
Alvimopan Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
Budesonide CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Any patient receiving both budesonide and a moderate CYP3A4 inhibitor should be monitored closely for signs/symptoms of corticosteroid excess.
Colchicine CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of colchicine. Reduce colchicine dose (for gout flares: to 1.2 mg x 1 dose, with next dose no sooner than 3 days later; for Familial Mediterranean Fever: to no more than 1.2 mg/day) when using in combination with a moderate CYP3A4 inhibitor such as erythromycin or verapamil. Increase monitoring for colchicine-related toxicity when using such combinations. Use extra caution in patients with impaired renal and/or hepatic function.
Everolimus CYP3A4 Inhibitors (Moderate)such as clotrimazole may increase the serum concentration of everolimus. The prescribing information for the Afinitor branded everolimus product lists indication-specific recommendations for managing this interaction.
Fentanyl CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of fentanyl. Concurrent use of fentanyl with any CYP3A4 inhibitor may result in increased fentanyl concentrations and could increase or prolong adverse effects, including potentially fatal respiratory depression. Patients receiving fentanyl and any CYP3A4 inhibitor should be closely monitored for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate.
Halofantrine CYP3A4 Inhibitors (Moderate) such as clotrmazole may increase the serum concentration of halofantrine. Extreme caution, with possibly increased monitoring of cardiac status (e.g., ECG), should be used with concurrent use of halofantrine with any moderate CYP3A4 inhibitor(s).
Lurasidone CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of lurasidone. Limit adult lurasidone dose to 40 mg/day in patients receiving a moderate CYP3A4 inhibitor.
Ranolazine CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of ranolazine. Limit the ranolazine dose to a maximum of 500mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). Monitor for increased effects/toxicity of ranolazine during concomitant use.
Tacrolimus The antifungal, Clotrimazole, may increase serum concentrations of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Clotrimazole therapy is initiated, discontinued or altered.
Tamsulosin Clotrimazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clotrimazole is initiated, discontinued, or dose changed.
Tolterodine Clotrimazole may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tolvaptan CYP3A4 Inhibitors (Moderate) may increase the serum concentration of tolvaptan. Coadministration of a strong CYP3A4 inhibitor with tolvaptan is contraindicated.
Tramadol Clotrimazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Trazodone The CYP3A4 inhibitor, Clotrimazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Clotrimazole is initiated, discontinued or dose changed.
食物相互作用
Not Available

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