Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.14-alpha Demethylase Inhibitors: Compounds that specifically inhibit STEROL 14-DEMETHYLASE. A variety of azole-derived ANTIFUNGAL AGENTS act through this mechanism.Miconazole: An imidazole antifungal agent that is used topically and by intravenous infusion.Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.Cytochrome P-450 CYP3A: A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Clotrimazole: 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.Sucralfate: A basic aluminum complex of sulfated sucrose.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Itraconazole: A triazole antifungal agent that inhibits cytochrome P-450-dependent enzymes required for ERGOSTEROL synthesis.Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal CANDIDIASIS and cryptococcal MENINGITIS in AIDS.Azoles: Five membered rings containing a NITROGEN atom.Econazole: An imidazole derivative that is commonly used as a topical antifungal agent.Sterol 14-Demethylase: An NADPH-dependent P450 enzyme that plays an essential role in the sterol biosynthetic pathway by catalyzing the demethylation of 14-methyl sterols such as lanosterol. The enzyme acts via the repeated hydroxylation of the 14-methyl group, resulting in its stepwise conversion into an alcohol, an aldehyde and then a carboxylate, which is removed as formic acid. Sterol 14-demethylase is an unusual cytochrome P450 enzyme in that it is found in a broad variety of organisms including ANIMALS; PLANTS; FUNGI; and protozoa.Candida: A genus of yeast-like mitosporic Saccharomycetales fungi characterized by producing yeast cells, mycelia, pseudomycelia, and blastophores. It is commonly part of the normal flora of the skin, mouth, intestinal tract, and vagina, but can cause a variety of infections, including CANDIDIASIS; ONYCHOMYCOSIS; vulvovaginal candidiasis (CANDIDIASIS, VULVOVAGINAL), and thrush (see CANDIDIASIS, ORAL). (From Dorland, 28th ed)Area Under Curve: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Malassezia: A mitosporic fungal genus that causes a variety of skin disorders. Malassezia furfur (Pityrosporum orbiculare) causes TINEA VERSICOLOR.Oxidoreductases, N-DemethylatingLoratadine: A second-generation histamine H1 receptor antagonist used in the treatment of allergic rhinitis and urticaria. Unlike most classical antihistamines (HISTAMINE H1 ANTAGONISTS) it lacks central nervous system depressing effects such as drowsiness.Amphotericin B: Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.Ergosterol: A steroid of interest both because its biosynthesis in FUNGI is a target of ANTIFUNGAL AGENTS, notably AZOLES, and because when it is present in SKIN of animals, ULTRAVIOLET RAYS break a bond to result in ERGOCALCIFEROL.Cross-Over Studies: Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)Butyrophenones: Compounds containing phenyl-1-butanone.TriazolesBiotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.Dermatomycoses: Superficial infections of the skin or its appendages by any of various fungi.Triazolam: A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries.Candida albicans: A unicellular budding fungus which is the principal pathogenic species causing CANDIDIASIS (moniliasis).Flucytosine: A fluorinated cytosine analog that is used as an antifungal agent.Candidiasis, Vulvovaginal: Infection of the VULVA and VAGINA with a fungus of the genus CANDIDA.Terfenadine: A selective histamine H1-receptor antagonist devoid of central nervous system depressant activity. The drug was used for ALLERGY but withdrawn due to causing LONG QT SYNDROME.Dealkylation: The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Midazolam: A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Mixed Function Oxygenases: Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.Troleandomycin: A macrolide antibiotic that is similar to ERYTHROMYCIN.PiperazinesHair Preparations: Hair grooming, cleansing and modifying products meant for topical application to hair, usually human. They include sprays, bleaches, dyes, conditioners, rinses, shampoos, nutrient lotions, etc.Dermatitis, Seborrheic: A chronic inflammatory disease of the skin with unknown etiology. It is characterized by moderate ERYTHEMA, dry, moist, or greasy (SEBACEOUS GLAND) scaling and yellow crusted patches on various areas, especially the scalp, that exfoliate as dandruff. Seborrheic dermatitis is common in children and adolescents with HIV INFECTIONS.Lice Infestations: Parasitic attack or subsistence on the skin by members of the order Phthiraptera, especially on humans by Pediculus humanus of the family Pediculidae. The hair of the head, eyelashes, and pubis is a frequent site of infestation. (From Dorland, 28th ed; Stedman, 26th ed)Pediculus: Lice of the genus Pediculus, family Pediculidae. Pediculus humanus corporus is the human body louse and Pediculus humanus capitis is the human head louse.Scalp DermatosesSelenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of GLUTATHIONE PEROXIDASE.Dandruff: Excessive shedding of dry scaly material from the scalp in humans.Scalp: The outer covering of the calvaria. It is composed of several layers: SKIN; subcutaneous connective tissue; the occipitofrontal muscle which includes the tendinous galea aponeurotica; loose connective tissue; and the pericranium (the PERIOSTEUM of the SKULL).4-Aminopyridine: One of the POTASSIUM CHANNEL BLOCKERS, with secondary effect on calcium currents, which is used mainly as a research tool and to characterize channel subtypes.Blastomycosis: A fungal infection that may appear in two forms: 1, a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2, chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung.Cryptococcosis: Infection with a fungus of the species CRYPTOCOCCUS NEOFORMANS.Arthrodermataceae: A family of ascomycetous fungi, order Onygenales, characterized by smooth ascospores. Genera in the family include Arthroderma, Keratinomyces, and Ctenomyces. Several well-known anamorphic forms are parasitic upon the skin.Blastomyces: A genus of onygenacetous mitosporic fungi whose perfect state is Ajellomyces (see ONYGENALES). The species Blastomyces dermatitidis (perfect state Ajellomyces dermatitidis) causes blastomycosis.

Cytochrome P-450 1A1 expression in human small bowel: interindividual variation and inhibition by ketoconazole. (1/766)

Human cytochrome P-450 1A1 (CYP1A1) is located primarily in extrahepatic tissues. To begin the characterization of this enzyme in the small intestine, we screened a bank of 18 human small intestinal microsomal preparations for CYP1A1 catalytic [(7-ethoxyresorufin O-deethylase (EROD)] activity and protein content. Although EROD activity was below detectable limits in 12 of the preparations, 6 exhibited measurable activity (1.4-123.5 pmol/min/mg), some exceeding that for 2 human liver microsomal preparations (11.0 and 26.4 pmol/min/mg). This variation was not due to variable quality of the preparations because each sample displayed readily detectable CYP3A4 catalytic activity and immunoreactive protein. We inadvertently found that intestinal EROD activity was inhibitable by ketoconazole at a concentration commonly believed to selectively inhibit CYP3A4. The possibility that CYP3A4 metabolizes 7-ethoxyresorufin was excluded because there was no correlation between intestinal CYP3A4 catalytic and EROD activity, and cDNA-expressed human CYP3A4 exhibited no EROD activity. Moreover, CYP1A1 immunoreactive protein was most abundant in the three intestinal preparations with the highest EROD activities, and the mean apparent Ki of ketoconazole observed for these three preparations (40 nM) was essentially identical with that for cDNA-expressed human CYP1A1 (37 nM). In summary, there is large interindividual variation in CYP1A1 expression in human small bowel, and ketoconazole is not a selective CYP3A4 inhibitor in in vitro metabolism studies involving intestinal tissue obtained from some individuals. These observations raise the possibility that in vivo drug interactions involving ketoconazole could result from CYP1A1 inhibition in the intestine in some individuals.  (+info)

Quantitative prediction of metabolic inhibition of midazolam by itraconazole and ketoconazole in rats: implication of concentrative uptake of inhibitors into liver. (2/766)

To evaluate the extent of drug-drug interaction concerning metabolic inhibition in the liver quantitatively, we tried to predict the plasma concentration increasing ratio of midazolam (MDZ) by itraconazole (ITZ) or ketoconazole (KTZ) in rats. MDZ was administered at a dose of 10 mg/kg through the portal vein at 60 min after bolus administration of 20 mg/kg ITZ or during 0.33 mg/h/body of KTZ infusion. The ratio values in the area under the plasma concentration curve of MDZ in the presence of ITZ and KTZ was 2.14 and 1.67, respectively. The liver-unbound concentration to plasma-unbound concentration ratios of ITZ and KTZ were 11 approximately 14 and 1.3, respectively, suggesting a concentrative uptake of both drugs into the liver. ITZ and KTZ competitively inhibited the oxidative metabolism of MDZ in rat liver microsomes, and Ki values of ITZ and KTZ were 0.23 microM and 0.16 microM, respectively. We predicted the ratio values of MDZ in the presence of ITZ and KTZ, using Ki values and unbound concentrations of both drugs in the plasma or liver. The predicted ratio values in the presence of ITZ or KTZ calculated by using unbound concentration in the plasma were 1.03 approximately 1.05 and 1.39, whereas those calculated using unbound concentration in the liver were 1.73 approximately 1.97 and 1.51, respectively, which were very close to the observed ratio values. These findings indicated the necessity to consider the concentrative uptake of inhibitors into the liver for the quantitative prediction of the drug-drug interactions concerning metabolic inhibition in the liver.  (+info)

In vitro metabolism of quinidine: the (3S)-3-hydroxylation of quinidine is a specific marker reaction for cytochrome P-4503A4 activity in human liver microsomes. (3/766)

The aim of this study was to evaluate the (3S)-3-hydroxylation and the N-oxidation of quinidine as biomarkers for cytochrome P-450 (CYP)3A4 activity in human liver microsome preparations. An HPLC method was developed to assay the metabolites (3S)-3-hydroxyquinidine (3-OH-Q) and quinidine N-oxide (Q-N-OX) formed during incubation with microsomes from human liver and from Saccharomyces cerevisiae strains expressing 10 human CYPs. 3-OH-Q formation complied with Michaelis-Menten kinetics (mean values of Vmax and Km: 74.4 nmol/mg/h and 74.2 microM, respectively). Q-N-OX formation followed two-site kinetics with mean values of Vmax, Km and Vmax/Km for the low affinity isozyme of 15.9 nmol/mg/h, 76.1 microM and 0.03 ml/mg/h, respectively. 3-OH-Q and Q-N-OX formations were potently inhibited by ketoconazole, itraconazole, and triacetyloleandomycin. Isozyme specific inhibitors of CYP1A2, -2C9, -2C19, -2D6, and -2E1 did not inhibit 3-OH-Q or Q-N-OX formation, with Ki values comparable with previously reported values. Statistically significant correlations were observed between CYP3A4 content and formations of 3-OH-Q and Q-N-OX in 12 human liver microsome preparations. Studies with yeast-expressed isozymes revealed that only CYP3A4 actively catalyzed the (3S)-3-hydroxylation. CYP3A4 was the most active enzyme in Q-N-OX formation, but CYP2C9 and 2E1 also catalyzed minor proportions of the N-oxidation. In conclusion, our studies demonstrate that only CYP3A4 is actively involved in the formation of 3-OH-Q. Hence, the (3S)-3-hydroxylation of quinidine is a specific probe for CYP3A4 activity in human liver microsome preparations, whereas the N-oxidation of quinidine is a somewhat less specific marker reaction for CYP3A4 activity, because the presence of a low affinity enzyme is demonstrated by different approaches.  (+info)

Metabolism of the antimalarial endoperoxide Ro 42-1611 (arteflene) in the rat: evidence for endoperoxide bioactivation. (4/766)

Ro 42-1611 (arteflene) is a synthetic endoperoxide antimalarial. The antimalarial activity of endoperoxides is attributed to iron(II)-mediated generation of carbon-centered radicals. An alpha, beta-unsaturated ketone (enone; 4-[2',4' bis(trifluoromethyl)phenyl]-3-buten-2-one), obtained from arteflene by reaction with iron(II), was identified previously as the stable product of a reaction that, by inference, also yields a cyclohexyl radical. The activation of arteflene in vivo has been characterized with particular reference to enone formation. [14C]Arteflene (35 micromol/kg) was given i.v. to anesthetized and cannulated male rats: 42.2 +/- 7.0% (mean +/- S.D., n = 7) of the radiolabel was recovered in bile over 5 h. In the majority of rats, the principal biliary metabolites were 8-hydroxyarteflene glucuronide (14.2 +/- 3. 9% dose, 0-3 h) and the cis and trans isomers of the enone (13.5 +/- 4.6% dose, 0-3 h). In conscious rats, 15.3 +/- 1.6% (mean +/- S.D., n = 8) of the radiolabel was recovered in urine over 24 h. The principal urinary metabolite appeared to be a glycine conjugate of a derivative of the enone. Biliary excretion of the glucuronide, but not of the enones, was inhibited by ketoconazole. 8-Hydroxyarteflene was formed extensively by rat and human liver microsomes but no enone was found. Bioactivation is a major pathway of arteflene's metabolism in the rat. Although the mechanism of in vivo bioactivation is unclear, the reaction is not catalyzed by microsomal cytochrome P-450 enzymes.  (+info)

Effects of azole antifungal drugs on the transition from yeast cells to hyphae in susceptible and resistant isolates of the pathogenic yeast Candida albicans. (5/766)

Oral infections caused by the yeast Candida albicans are some of the most frequent and earliest opportunistic infections in human immunodeficiency virus-infected patients. The widespread use of azole antifungal drugs has led to the development of drug resistance, creating a major problem in the treatment of yeast infections in AIDS patients and other immunocompromised individuals. Several molecular mechanisms that contribute to drug resistance have been identified. In C. albicans, the ability to morphologically switch from yeast cells (blastospores) to filamentous forms (hyphae) is an important virulence factor which contributes to the dissemination of Candida in host tissues and which promotes infection and invasion. A positive correlation between the level of antifungal drug resistance and the ability to form hyphae in the presence of azole drugs has been identified. Under hypha-inducing conditions in the presence of an azole drug, resistant clinical isolates form hyphae, while susceptible yeast isolates do not. This correlation is observed in a random sample from a population of susceptible and resistant isolates and is independent of the mechanisms of resistance. 35S-methionine incorporation suggests that growth inhibition is not sufficient to explain the inhibition of hyphal formation, but it may contribute to this inhibition.  (+info)

YM116, 2-(1H-imidazol-4-ylmethyl)-9H-carbazole, decreases adrenal androgen synthesis by inhibiting C17-20 lyase activity in NCI-H295 human adrenocortical carcinoma cells. (6/766)

The concentrations of androstenedione and dehydroepiandrosterone, products of C17-20 lyase, in the medium after a 6-hr incubation of NCI-H295 cells were decreased by YM116 (2-(1H-imidazol-4-ylmethyl)-9H-carbazole) (IC50: 3.6 and 2.1 nM) and ketoconazole (IC50: 54.9 and 54.2 nM). 17Alpha-hydroxyprogesterone, a product of 17alpha-hydroxylase, was increased by YM116 (1-30 nM) and by ketoconazole (10-300 nM) and then was decreased at higher concentrations of both agents (IC50: 180 nM for YM116, 906 nM for ketoconazole), indicating that YM116 and ketoconazole were 50- and 16.5-fold more specific inhibitors of C17-20 lyase, respectively, than 17alpha-hydroxylase. Compatible with these findings, progesterone, a substrate of 17alpha-hydroxylase, was increased by these agents. Cortisol production was inhibited by YM116 and ketoconazole (IC50: 50.4 and 80.9 nM, respectively). YM116 was a 14-fold more potent inhibitor of androstenedione production than cortisol production, whereas ketoconazole was a nonselective inhibitor of the production of both steroids. YM116 and ketoconazole inhibited the C17-20 lyase activity in human testicular microsomes (IC50: 4.2 and 17 nM, respectively). These results demonstrate that YM116 reduces the synthesis of adrenal androgens by preferentially inhibiting C17-20 lyase activity.  (+info)

Metabolic interactions between mibefradil and HMG-CoA reductase inhibitors: an in vitro investigation with human liver preparations. (7/766)

AIMS: To determine the effects of mibefradil on the nletabolism in human liver microsomal preparations of the HMG-CoA reductase inhibitors simvastatin, lovastatin, atorvastatin, cerivastatin and fluvastatin. METHODS: Metabolism of the above five statins (0.5, 5 or 10 microM), as well as of specific CYP3A4/5 and CYP2C8/9 marker substrates, was examined in human liver microsomal preparations in the presence and absence of mibefradil (0.1-50 microM). RESULTS: Mibefradil inhibited, in a concentration-dependent fashion, the metabolism of the four statins (simvastatin, lovastatin, atorvastatin and cerivastatin) known to be substrates for CYP3A. The potency of inhibition was such that the IC50 values (<1 microM) for inhibition of all of the CYP3A substrates fell within the therapeutic plasma concentrations of mibefradil, and was comparable with that of ketoconazole. However, the inhibition by mibefradil, unlike that of ketoconazole, was at least in part mechanism-based. Based on the kinetics of its inhibition of hepatic testosterone 6beta-hydroxylase activity, mibefradil was judged to be a powerful mechanism-based inhibitor of CYP3A4/5, with values for Kinactivation, Ki and partition ratio (moles of mibefradil metabolized per moles of enzyme inactivated) of 0.4 min(-1), 2.3 microM and 1.7, respectively. In contrast to the results with substrates of CYP3A, metabolism of fluvastatin, a substrate of CYP2C8/9, and the hydroxylation of tolbutamide, a functional probe for CYP2C8/9, were not inhibited by mibefradil. CONCLUSION: Mibefradil, at therapeutically relevant concentrations, strongly suppressed the metabolism in human liver microsomes of simvastatin, lovastatin, atorvastatin and cerivastatin through its inhibitory effects on CYP3A4/5, while the effects of mibefradil on fluvastatin, a substrate for CYP2C8/9, were minimal in this system. Since mibefradil is a potent mechanism-based inhibitor of CYP3A4/5, it is anticipated that clinically significant drug-drug interactions will likely ensue when mibefradil is coadministered with agents which are cleared primarily by CYP3A-mediated pathways.  (+info)

Effect of selected antimalarial drugs and inhibitors of cytochrome P-450 3A4 on halofantrine metabolism by human liver microsomes. (8/766)

Halofantrine (HF) is used in the treatment of uncomplicated multidrug-resistant Plasmodium falciparum malaria. Severe cardiotoxicity has been reported to be correlated with high plasma concentrations of HF but not with that of its metabolite N-debutylhalofantrine. The aim of this study was to investigate the effects of other antimalarial drugs and of ketoconazole, a typical cytochrome P-450 3A4 inhibitor, on HF metabolism by human liver microsomes. Antimalarial drug inhibitory effects were ranked as follows: primaquine > proguanil > mefloquine > quinine > quinidine > artemether > amodiaquine. Artemisine, doxycycline, sulfadoxine, and pyrimethamine showed little or no inhibition of HF metabolism. Mefloquine, quinine, quinidine, and ketoconazole used at maximal plasma concentrations inhibited N-debutylhalofantrine formation noncompetitively with Ki values of 70 microM, 49 microM, 62 microM, and 0.05 microM resulting in 7%, 49%, 26%, and 99% inhibition, respectively, in HF metabolism. In conclusion, we showed that quinine and quinidine coadministered with HF might inhibit its metabolism resulting in the potentiation of HF-induced cardiotoxicity in patients. This requires a close monitoring of ECG. For the same reasons, the concomitant administration of HF and ketoconazole must be avoided. By contrast, none of the other antimalarials studied inhibited HF metabolism and, by extrapolation, cytochrome P-450 3A4 activity.  (+info)

  • EXTINA ® Foam contains 2% ketoconazole in a thermolabile hydroethanolic foam in 50 g and 100 g containers ( 3 ). (
  • EXTINA ® (ketoconazole) Foam, 2% is indicated for the topical treatment of seborrheic dermatitis in immunocompetent patients 12 years of age and older. (
  • High doses of ketoconazole are sometimes used to treat Cushing syndrome (a condition that occurs when there is too much corticosteroid hormone in the body) and advanced prostate cancer (cancer of a male reproductive gland). (
  • The information provided here focuses on the use of ketoconazole to treat prostate cancer. (
  • Based on these antiandrogen and antiglucocorticoid effects, ketoconazole has been used with some success as a second-line treatment for certain forms of advanced prostate cancer and for the suppression of glucocorticoid synthesis in the treatment of Cushing's syndrome. (
  • Because of the anti-androgen effects of ketoconazole, some doctors prescribe it for off-label uses, such as treating prostate cancer, high blood levels of cortisol and excessive hair growth in women, known as hirsutism. (
  • In addition, ketoconazole has been shown to have direct cell killing action on prostate cancer cells [ 6 ]. (
  • No prior ketoconazole, abiraterone, aminoglutethimide or corticosteroids for treatment of progressive prostate cancer. (
  • It has always been assumed that Ketoconazole, when used for the treatment of men with metastatic castration resistant prostate cancer (mCRPC), would not be as potent as abiraterone (Zytiga), but there has never been any head to head comparison to demonstrate this assumption! (
  • Some men with advanced prostate cancer have been given the antifungal treatment Ketoconazole (Keto) as a second line hormone treatment. (
  • Zytiga (abiraterone acetate) and Ketoconazole (keto) are both widely used in prostate cancer therapy to treat men with advanced prostate cancer. (
  • The use of Ketoconazole (Keto) in men with advanced prostate cancer is not considered mainstream, however there is clear evidence that it does reduce PSA in men with castrate resistant prostate cancer. (
  • OBJECTIVES: I. Determine the clinical benefit of two combination chemotherapy regimens, paclitaxel, etoposide, and estramustine vs ketoconazole, doxorubicin, vinblastine, and estramustine in patients with androgen independent prostate cancer, as measured by prostate specific antigen (PSA)-based response rate, time to progression, and overall survival. (
  • This phase II study was designed to assess responses to blocking multiple steps in androgen synthesis with inhibitors of CYP17A1 (ketoconazole) and type I and II 5α-reductases (dutasteride) in patients with castration-resistant prostate cancer (CRPC). (
  • For example, ketoconazole can increase the plasma concentration of oral midazolam (Versed), triazolam (Halcion), and alprazolam (Xanax), which can increase the severity of lethargy commonly caused by these medications. (
  • In 2013 the European Medicines Agency's Committee on Medicinal Products for Human Use (CHMP) recommended that a ban be imposed on the use of oral ketoconazole for systemic use in humans throughout the European Union, after concluding that the risk of serious liver injury from systemic ketoconazole outweighs its benefits. (
  • The oral formulation of ketoconazole was discontinued in Australia in 2013 and in China in 2015. (
  • Cite this: FDA, EMA Come Down Hard on Oral Ketoconazole - Medscape - Jul 26, 2013. (
  • Response of scalp psoriasis to oral ketoconazole. (
  • A randomised double-blind placebo-controlled study showed improvement of scalp psoriasis with oral ketoconazole, although the study had to be stopped before completion because of the possibility of drug toxicity. (
  • Since ketoconazole is a potent inhibitor of cytochrome P450 isoenzymes in the liver, it can increase concentrations and potentiate the effects of some drugs, such as cyclosporine, phenytoin, oral hypoglycemics, and oral anticoagulants [ 7 ]. (
  • Comparative study of oral and topical ketoconazole therapy in pityriasis versicolor. (
  • RESULTS: On global assessment, after 2 weeks of start of therapy, 18 (90%) out of 20 patients treated with oral ketoconazole were cured while 2 patients had considerable residual disease. (
  • Do this, check your testosterone levels, take oral ketoconazole for 2 weeks, then check your testosterone levels and tell us. (
  • A single oral dose of 400 mg ketoconazole , a broad-spectrum antifungal drug, administered orally to 5 young men induced a drop in serum and saliva testosterone into the range of hypogonadism , while LH, FSH and prolactin levels remained unchanged. (
  • Large oral doses of ketoconazole (the active ingredient in ketoconazole foam) can cause liver problems and hormonal imbalances, although these problems have not been seen with ketoconazole products applied to the skin like ketoconazole foam. (
  • FDA has decided to limit the use of oral ketoconazole (Nizoral) to life-threatening mycoses because the drug can cause severe liver injuries and adrenal gland problems, according to an FDA statement released at the end of July. (
  • Healthcare professionals should assess the liver status of the patient before starting oral ketoconazole, and monitor serum ALT levels during treatment. (
  • In addition, there is the possibility of drug interactions with oral ketoconazole, which can be serious and potentially life-threatening, such as heart rhythm problems. (
  • Healthcare professionals and patients can report adverse events related to the use of oral ketoconazole to the FDA's MedWatch Safety Information and Adverse Event Reporting Program either online or by calling to request a reporting form at 1-800-332-1088. (
  • Ketoconazole Oral Suspension contains not less than 1.8 g and not more than 2.2 g of Ketoconazole in 100 mL of Oral Suspension. (
  • Ketoconazole causes an increase in the levels of most protease inhibitors, as it is an inhibitor of the CYP3A4 enzyme. (
  • We investigated the effects of ketoconazole, a p-glycoprotein inhibitor, and rifampicin, a p-glycoprotein inducer, on the pharmacokinetics of nintedanib. (
  • Inhibitor constant values generated for dextropropoxyphene (3.5 μM), fluconazole (202 μM), ketoconazole (0.66 μM), and methadone (0.32 μM) predicted 1.60- to 3.66-fold increases in the area under the drug plasma concentration-time curve ratio for COD in vivo. (
  • Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants, and by quinidine and ketoconazole: a model system to predict drug interactions in vivo. (
  • Ketoconazole was a much less potent inhibitor (mean Ki = 10.3 microM). (
  • In this exploratory single-arm phase II study, we assessed the efficacy of blocking two steps in androgen synthesis by combining a dual SRD5A1/SRD5A2 inhibitor (dutasteride) with a CYP17A1 inhibitor (ketoconazole) in CRPC. (
  • Ketoconazole has therapeutic effects against dermatophytosis, superficial candidiasis, and paracoccidioidomycosis. (
  • Recently topical use of 2% Ketoconazole solution has been reported to have a therapeutic effect on androgenic alopecia. (
  • Viagra and ketoconazole interaction - Although recommendations for patient specific detailed therapeutic plan c monitoring parameters to determine which treatments for psoriasis. (
  • Ketoconazole is routinely assigned therapeutic drug monitoring due to its high toxicity and narrow therapeutic range. (
  • This Certified Spiking Solution® is suitable as starting material for calibrators, controls, or linearity standards for therapeutic drug monitoring or clinical and diagnostic testing of ketoconazole in patient blood, serum, or plasma samples by HPLC or LC-MS/MS. (
  • Do not stop taking ketoconazole without talking to your doctor. (
  • If you stop taking ketoconazole too soon, your infection may come back after a short time. (
  • Ketoconazole kills fungi and yeasts by interfering with their cell membranes. (
  • Ketoconazole has activity against many kinds of fungi that may cause human disease, such as Candida, Histoplasma, Coccidioides, and Blastomyces (although it is not active against Aspergillus). (
  • While ketoconazole blocks the synthesis of the sterol ergosterol in fungi, in humans, at high dosages (>800 mg/day), it potently inhibits the activity of several enzymes necessary for the conversion of cholesterol to steroid hormones suchas testosterone and cortisol. (
  • Ketoconazole, commonly known by the brand name Nizoral®, is used in cats and dogs to treat infections caused by fungi. (
  • Pharmacology - At usual doses and serum concentrations, ketoconazole is fungistatic against susceptible fungi. (
  • Whereas fluconazole and ketoconazole inhibited UGT2B4- and UGT2B7-catalyzed COD glucuronidation to a similar extent, inhibition by dextropropoxyphene and methadone resulted largely from an effect on UGT2B4. (
  • Interactions with dextropropoxyphene, fluconazole, ketoconazole, and methadone potentially affect the intensity and duration of COD analgesia. (
  • Although newer antifungal agents (fluconazole, itra-conazole) have advantages over ketoconazole-usually less toxicity and/or enhanced effi-cacy-ketoconazole is significantly less expensive. (
  • Activity of fluconazole (UK 49,858) and ketoconazole against Candida albicans in vitro and in vivo. (
  • Fluconazole (UK 49,858), a new orally administered bis-triazole, was compared with ketoconazole for activity in synthetic broth dilution susceptibility tests against Candida albicans and also in treatment of experimental systemic candidal infections in rats. (
  • In vitro studies indicated that fluconazole activity is less sensitive to acidic medium than is that of ketoconazole. (
  • At physiologic pH, fluconazole was approximately 16-fold less active than ketoconazole against 35 representative isolates of C. albicans. (
  • With an inoculum sufficient to kill 29 of 38 sham-treated animals, only 1 of 18 animals treated with 0.5 mg of fluconazole per kg per day died compared with 13 of 20 animals treated with 10.0 mg of ketoconazole per kg per day. (
  • However, in comparing results between drugs, ketoconazole was 16-fold more active in vitro and fluconazole was 20-fold more active in vivo. (
  • Nursing mothers should probably avoid breastfeeding while using ketoconazole. (
  • This case describes the increased anticoagulation effect associated with the use of high-dose ketoconazole. (
  • The Naranjo probability scale revealed a probable adverse reaction of increased anticoagulant effect associated with high dose ketoconazole. (
  • Alternatives to AD are secondary hormonal interventions such as high-dose ketoconazole (HDK), aminoglutethimide, or diethylstilbestrol [ 2 , 3 ]. (
  • Ketoconazole suppresses hormone synthesis and has been used to treat conditions associated with excessive production of the hormone cortisone from the adrenal gland such as hyperadrenocorticism ( Cushing's Disease ). (
  • Ketoconazole inhibits the hormone synthesis in animals and treated animals have decreased levels of cortisol (cortisone), testosterone and other sex hormones. (
  • The exact mechanism for these effects have not been deter-mined, but may be due to ketoconazole interfering with ergosterol synthesis. (
  • Ketoconazole also has endocrine effects as steroid synthesis is directly inhibited by blocking several P-450 enzyme systems. (
  • Consistent with this mechanism, inhibitors of CYP17A1 (ketoconazole or the more potent abiraterone), the enzyme that mediates androgen precursor synthesis, are active in CRPC, but responses are partial and transient. (
  • Ketoconazole may cause liver damage, sometimes serious enough to require liver transplantation or to cause death. (
  • Do not drink any alcoholic beverages during your treatment with ketoconazole because drinking alcoholic beverages may increase the risk that you will develop liver damage. (
  • Taking ketoconazole may cause liver damage. (
  • If you drink large amounts of alcohol, if you take medications that can have negative effects on the liver or if you have ever had liver disease, tell your doctor before taking ketoconazole, instructs the National Center for Biotechnology Information's PubMed Health website. (
  • In rare cases, ketoconazole can cause severe liver damage. (
  • Contact your veterinarian if your pet experiences lack of appetite, vomiting, diarrhea, liver toxicity (jaundice - yellowing of gums, skin, or eyes) or bleeding problems while being treated with ketoconazole. (
  • Ketoconazole is powerful enough to eliminate severe infections including dermatitis, ringworm, and seborrhea. (
  • The other four sections deal with ketoconazole specifically and include the pharmacology of the drug, clinical experience in the treatment of superficial and deep mycoses, and some practical aspects of treatment. (
  • Treatment of mice bearing GBM with Ketoconazole and Posaconazole increased their survival, reduced tumor cell proliferation, and decreased tumor metabolism. (
  • For seborrhea treatment, ketoconazole foam is applied twice a day for four weeks. (
  • the prescribing information for ketoconazole foam does not mention the possibility of more than one treatment. (
  • The scientists have separately discovered Ketoconazole to boost the end result significantly of treatment in pattern baldness. (
  • Ketoconazole is also used clinically for the medical treatment of hyperadrenocorticism in dogs (and sometimes cats). (
  • Ketoconazole can also be used to reduce the doses and costs of cyclosporine treatment by increasing cyclosporine drug metabolism. (
  • What Other Drugs Interact with Ketoconazole? (
  • Ketoconazole has severe interactions with at least 33 different drugs. (
  • Ketoconazole has serious interactions with at least 202 different drugs. (
  • Ketoconazole has moderate interactions with at least 241 different drugs. (
  • Ketoconazole belongs to a general class of drugs known as antifungal drugs. (
  • Ketoconazole interferes with the metabolism of several drugs including cyclosporine. (
  • Consult with your veterinarian to determine if other drugs your pet is receiving could interact with ketoconazole. (
  • 2 For some people, taking ketoconazole cola helps to increase the stomach acidity and improve the drugs absorption. (
  • In any case, the risk of hepatotoxicity with ketoconazole limits its use in all of these indications, especially in those that are benign such as hirsutism. (
  • tell your doctor and pharmacist if you are allergic to ketoconazole or any other medications, creams, or shampoos. (
  • You should not use this medicine if you are allergic to ketoconazole. (
  • Do not use Nizoral (ketoconazole) if you are allergic to Ketoconazole or are also taking triazolam (Halcion). (
  • They do not apply to topical formulations of ketoconazole in creams, shampoos, foams, and gels. (
  • At least one study has been performed showing that ketoconazole may be useful in temporarily reducing erectile function in postoperative penile surgery patients. (
  • Ketoconazole was not detected in plasma in 39 patients who shampooed 4-10 times per week for 6 months, or in 33 patients who shampooed 2-3 times per week for 3-26 months (mean: 16 months). (
  • further, patients may initiate bisphosphonate therapy at the time of ketoconazole initiation. (
  • Ketoconazole should not be taken by patients taking nevirapine ( Viramune ), due to a dramatic reduction in ketoconazole levels. (
  • Patients with locally advanced or metastatic breast cancer and with measurable primary breast tumor will be treated with 70mg docetaxel combined with ketoconazole. (
  • The authors' assessments of the toxicity of ketoconazole are valuable because they were derived from the careful observation of 52 patients. (
  • The mediocre safety profile associated with ketoconazole has relegated this drug to second-line therapy status, while high-prescribing physicians choose higher-efficacy treatments, such as terbinafine and itraconazole, for most patients, as noted from GlobalData's primary research. (
  • Ketoconazole is contraindicated in patients who have shown hypersensitivity to the drug or excipients of the formulation. (
  • Two additional isolates (K-1 and K-3) recovered from patients who had failed ketoconazole therapy were 32- to 64-fold more resistant than the median of each drug for other isolates. (
  • Ketoconazole is not effective against infections caused by bacteria, parasites (intestinal worms), mites, or viruses. (
  • Nizoral (ketoconazole) does not treat viral infections such as a common cold or flu. (
  • This wide interpatient varia-tion may have significant clinical implications from both a toxicity and efficacy stand-point, particularly since ketoconazole is often used in life-threatening infections and as-says for measuring serum levels are not readily available. (
  • When your symptoms improve, continue taking Nizoral (ketoconazole) for the entire time it is prescribed to you because your infection may not have been treated completely as soon as you notice your symptoms improved. (
  • Minoxidil is better to use than Ketoconazole from my experience. (
  • To compare the stimulatory effect of Ketoconazole, Minoxidil, and Minoxidil with Tretinoin on hair growth in a mouse model. (
  • These mice were divided into four groups each of five treated with topical application of ethanol 95%, Ketoconazole solution 2%, Minoxidil solution 5%, and Minoxidil with Tretinoin solution 0.1%, respectively. (
  • The results demonstrated that Ketoconazole, Minoxidil, and Minoxidil with Tretinoin had a significant stimulatory effect on hair growth compared with the control group and Minoxidil was the most effective drug among them. (
  • Another study was performed in 1998 to compared the effects of ketoconazole and minoxidil, another material that helps promote hair growth. (
  • An early research study in 1998 compared the result of Minoxidil as well as Ketoconazole on pattern baldness of male and hair development. (
  • The scientists found that the hair density and percentage of hair roots in the growth stage, i.e., anagen stage, enhanced practically in a similar way by both Minoxidil and Ketoconazole. (
  • Another clinical study has actually concentrated on assessing the efficiency of Ketoconazole when utilized combined with Minoxidil or Finasteride. (
  • Ketoconazole is a pregnancy category C drug because animal testing has shown it to cause teratogenesis when administered in high doses. (
  • Ketoconazole is a prescription drug and can only be obtained from a veterinarian or by prescription from a veterinarian. (
  • Cyclosporine is an expensive drug and Ketoconazole is sometimes used to allow for a reduction in dose of the drug cyclosporine. (
  • Because of a possible beneficial effect of a combination of ketoconazole and a chemotherapeutic drug in multidrug resistant cancers, we examined a panel of 11 prostate carcinoma tissues for the expression of the MDR1 gene by an RNA-PCR assay. (
  • Quality Drug Ketoconazole at Bargain Prices! (
  • Nizoral (ketoconazole, keto) is an older drug that has been used as a part of hormone therapy (ADT) for many years. (
  • Generic drug Ketoconazole is considered just as safe and effective as its brand-name equivalents such as Nizoral and Daktagold. (
  • Did you know that buying the generic drug Ketoconazole from IDM is much cheaper than buying the Nizoral or Daktagold brand drug? (
  • 1. CC-223 was studied in vitro for metabolism and drug-drug interactions (DDI), and in clinic for interaction with ketoconazole. (
  • The genetic basis of variation in drug response was investigated in individual Saccharomyces cerevisiae strains that exhibited different susceptibility to two antifungal agents: benomyl and ketoconazole. (
  • Ketoconazole absorption is enhanced in an acidic environment and should not be admin-istered (at the same time) with H 2 blockers or antacids (see Drug Interactions below). (
  • 1. Evaluate the clinical response rate of 70mg docetaxel with ketoconazole in metastatic breast cancer. (
  • We hypothesize that 70mg docetaxel co-administered with ketoconazole would result in similar clinical efficacy as conventional doses of docetaxel (75mg/m2 body surface area) in terms of clinical and pathological response rates in metastatic breast cancer. (
  • The primary objectives are to evaluate the clinical response rate of 70mg docetaxel with ketoconazole in metastatic breast cancer, and to evaluate the pathological response rate in the primary tumor following four cycles of docetaxel and ketoconazole. (
  • There are problems, however, with the authors' evaluation of the clinical responses to ketoconazole therapy. (