Ketoconazole and Talk:List of Registered Historic Places in Los Angeles: Difference between pages
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<!-- FAIR USE of Nizoral.gif: see image description page at http://en.wikipedia.org/wiki/Image:Nizoral.gif for rationale --> |
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{{Drugbox| |
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|IUPAC_name = <nowiki>1-[4-[4-[[</nowiki>(2''S'',4''R'')-2-(2,4-dichlorophenyl)-<br>2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]<br>phenyl]piperazin-1-yl]ethanone |
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| image=Ketoconazole2.png |
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| width=250 |
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| CAS_number=65277-42-1 |
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| ATC_prefix=J02 |
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| ATC_suffix=AB02 |
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| ATC_supplemental= {{ATC|D01|AC08}} {{ATC|G01|AF11}} |
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| PubChem=47576 |
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| DrugBank=APRD00401 |
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| C = 26 |H = 28 |Cl = 2 |N = 4 |O = 4 |
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| molecular_weight = 531.43 [[Gram|g]]/[[Mole (unit)|mol]] |
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| bioavailability= Variable |
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| protein_bound = 84 to 99% |
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| metabolism = [[Liver|Hepatic]] |
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| elimination_half-life= Biphasic: |
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*Initial phase: 2 [[hour]]s |
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*Terminal phase: 8 hours |
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| excretion = Biliary and [[Kidney|renal]] |
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| pregnancy_category = B3 <small>([[Australia|Au]])</small>, C <small>([[United States|U.S.]])</small> |
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| legal_status = [[Prescription drug|POM]] <small>([[United Kingdom|UK]], oral formulation)</small> |
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| routes_of_administration= Oral, [[topical]] |
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}} |
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'''Ketoconazole''' is a synthetic [[antifungal drug]] used to [[prophylaxis|prevent]] and treat skin and fungal infections, especially in [[Immune deficiency|immunocompromised]] patients such as those with [[AIDS]]. Due to its [[side-effect]] profile, it has been superseded by newer antifungals, such as [[fluconazole]] and [[itraconazole]].<ref>{{cite web | last = Lewis | first = Russell | title = Ketoconazole | url=http://www.doctorfungus.com/thedrugs/ketoconazole.htm | accessdate = 2007-09-18 }}</ref> Ketoconazole is sold commercially as an anti-[[dandruff]] [[shampoo]], branded '''[[Nizoral]]®''', by [[Janssen Pharmaceutica]]. |
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Ketoconazole is very [[lipophilic]], which leads to accumulation in fatty tissues. The less [[toxic]] and more effective triazole compounds [[fluconazole]] and [[itraconazole]] have largely replaced ketoconazole for internal use. Ketoconazole is best absorbed at highly [[acid]]ic levels, so [[antacid]]s or other causes of decreased [[stomach]] acid levels will lower the drug's absorption when taken orally. |
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==History== |
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Ketoconazole was discovered in 1976 and released in the early 1980s, and was one of the first available oral treatments for fungal infections ([[griseofulvin]] was available before ketoconazole). |
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== Usage == |
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Ketoconazole is usually prescribed for infections such as [[athlete's foot]], [[ringworm]], [[candidiasis]] (yeast infection or thrush), and [[jock itch]]. The over-the-counter [[shampoo]] version can also be used as a body wash for the treatment of [[tinea versicolor]]. |
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Ketoconazole is used to treat [[eumycetoma]], the fungal form of [[mycetoma]]. |
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The side-effects of ketoconazole are sometimes used to treat non-fungal problems. The decrease in [[testosterone]] caused by the drug makes it useful for treating [[prostate cancer]] and for preventing post-operative erections<ref> |
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{{cite journal | first = K. C. | last = Evans | coauthors = A. C. Peterson, H. E. Ruiz and R. A. Costabile | month = August | year = 2004 | title = Use of oral ketoconazole to prevent postoperative erections following penile surgery | journal = International Journal of Impotence Research | volume = 16| issue = 4 | pages = 346–349 | id = {{PMID|14973533}} | doi = 10.1038/sj.ijir.3901160 | url = http://www.nature.com/ijir/journal/v16/n4/full/3901160a.html}}</ref> |
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following penile surgery. Another use is the suppression of [[glucocorticoid]] synthesis, where it is used in the treatment of [[Cushing's disease]].<ref name=Cushing>{{cite journal | first = Paola | last = Loli | coauthors = Maria Elisa Berselli and Mariantonella Tagliaferri | year = 1986 | title = Use of ketoconazole in the treatment of Cushing's syndrome. | journal = Journal of Clinical Endocrinology & Metabolism | volume = 63 | issue = 6 | pages = 1365-71 | id = {{PMID|3023421}}}}</ref> These side effects have also been studied for use in reducing [[clinical depression|depressive]] symptoms<ref name=antidepressant_properties>{{cite journal | first = Owen M. | last = Wolkowitz | coauthors = Victor I. Reus | year = 1999 | title = Treatment of Depression With Antiglucocorticoid Drugs | journal = Psychosomatic Medicine | volume = 61 | issue = 5 | pages = 698-711 | id = {{PMID|10511017}} | url = http://www.psychosomaticmedicine.org/cgi/content/full/61/5/698 }}</ref> and [[drug addiction]];<ref name=anti-drug>{{cite journal | first = Nick E. | last = Goeders | coauthors = Rachel L. Peltiera and Glenn F. Guerin | month = December | year = 1998 | title = Ketoconazole reduces low dose cocaine self-administration in rats. | journal = Drug and Alcohol Dependence | volume = 53 | issue = 1 | pages = 67-77 | id = {{PMID|10933341}} | doi = 10.1016/S0376-8716(98)00108-2 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=10933341&dopt=ExternalLink}}</ref> however, it has not succeeded in either of these roles.<ref name=failed_for_depression>{{cite journal | first = Robert T. | last = Malison | coauthors = Amit Anand, Gregory H. Pelton, Paul Kirwin, Linda Carpenter, Christopher J. McDougle, George R. Heninger and Lawrence H. Price | month = October | year = 1999 | title = Limited Efficacy of Ketoconazole in Treatment-Refractory Major Depression. | journal = Journal of Clinical Psychopharmacology | volume = 19 | issue = 5 | pages = 466-470 | id = {{PMID|10505589}}}}</ref><ref name=failed_for_cocainism>{{cite journal | first = Amie S. | last = Ward | coauthors = Eric D. Collins, Margaret Haney, Richard W. Foltin and Marian W Fischman | month = November | year = 1998 | title = |
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Ketoconazole attenuates the cortisol response but not the subjective effects of smoked cocaine in humans. | journal = Behavioural Pharmacology | volume = 9 | issue = 7 | pages = 577-86 | id = {{PMID|9862083}} }}</ref> |
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Ketoconazole can be prescribed as a 200-mg pill, a 2% [[Cream (pharmaceutical)|cream]], a 2% [[gel]],a 2% [[foam]],or 2% [[shampoo]] for the treatment of [[dandruff]] or [[seborrhoeic dermatitis]], or as a 1% [[over-the-counter substance|over-the-counter]] shampoo (''Nizoral''). |
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Ketokanazole is also available as a topical mousse, using patented Versafoam technology, marketed under the brand name Ketomousse. In clinical studies, the Versafoam proved to be a superior mechanism of delivery to the shampoo. Currently it is only available in Europe. |
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The anti-dandruff shampoo is designed for people who have a more serious case of dandruff where symptoms include, but are not limited to constant non-stop flaking, and severe itchiness. |
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It is a [[Pregnancy category (pharmaceutical)|pregnancy category C]] drug because [[animal testing]] has shown it to cause [[teratogenesis]] in high dosages. Until recently, there were two human test cases on record (both during the treatment of [[Cushing's syndrome]])<ref name=pregnancy_1>{{cite journal | first = José Antonio | last = Amado | coauthors = Carlos Pesquera, Eva M. Gonzalez, Macarena Otero, Julio Freijanes, and Angel Alvarez | month = March | year = 1990 | title = Successful treatment with ketoconazole of Cushing's syndrome in pregnancy. | journal = Postgraduate Medical Journal | volume = 66 | issue = 773 | pages = 221-3 | id = {{PMID|2362890}}}}</ref><ref name=pregnancy_2>{{cite journal | first = Joris | last = Berwaerts | coauthors = Johan Verhelst, Charles Mahler and Roger Abs | month = June | year = 1999 | title = Cushing's syndrome in pregnancy treated by ketoconazole: case report and review of the literature. | journal = Gynecological Endocrinology | volume = 13 | issue = 3 | pages = 175-82 | id = {{PMID|10451809}} | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=10451809&dopt=ExternalLink}}</ref> and no adverse effects were reported, but this is not a broad enough data sample to draw any meaningful conclusions. To remedy this, Drs Kazy, Puhó and Czeizel of the Foundation for the Community Control of Hereditary Diseases in Budapest, Hungary decided to go through the Hungarian Case–Control Surveillance of Congenital Abnormalities, specifically the years 1980 through 1996; that was 22,843 cases and 38,151 controls. There were six infants with congenital abnormalities and twelve infants without whose mothers received ketoconazole. No group of birth defects was preferentially associated with use of ketoconazole.<ref name=Giant_Hungarian_Human_Birth_Defects_Study>{{cite journal | first = Zoltán | last = Kazy | coauthors = Erzsébet Puhó and Andrew E. Czeizel | month = March | year = 2005 | title = Population-based case–control study of oral ketoconazole treatment for birth outcomes | journal = Congenital Anomalies | volume = 45 | issue = 1 | pages = 5-8 | id = {{PMID|15737124}} | doi = 10.1111/j.1741-4520.2005.00053.x | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=15737124&dopt=ExternalLink}}</ref> |
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This medication is also sometimes prescribed by [[veterinarian]]s for use on pets, often as 200mg unflavored tablets that may need to be cut to smaller size for correct dosage.<ref>[http://petscriptions.com/index.php?level2=catalog&level3=item_detail&item_id=1209 Ketoconazole for Your Pet at Petscriptions<!-- Bot generated title -->]</ref> |
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==Method of action== |
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Ketoconazole is structurally similar to [[imidazole]], and interferes with the fungal synthesis of [[ergosterol]], a constituent of [[cell membrane]]s, as well as certain [[enzyme]]s. It is specific for fungi, as the equivalent [[mammal]]ian pathway, leading to the biosynthesis of [[cholesterol]], is not sensitive to ketoconazole. However, other mammalian [[cytochrome P450]] enzymes can be sensitive to ketoconazole, and inhibition of [[steroid hormone]] synthesis is a possible side effect of ketoconazole treatment. |
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As with all azole antifungal agents, ketoconazole works principally by inhibition of an [[enzyme]], [[cytochrome P450]] 14-alpha-demethylase (P45014DM). This enzyme is in the [[sterol]] [[biosynthesis]] pathway that leads from [[lanosterol]] to [[ergosterol]]. [[Fluconazole]] and [[itraconazole]] have been found to have a greater affinity for fungal cell membrane than ketoconazole, and thus lower doses of these azoles are required to kill fungi. |
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==Sensitive fungi== |
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Ketoconazole inhibits growth of [[dermatophyte]]s and [[yeast]] species such as ''[[Candida albicans]]''. No [[drug resistance|resistance]] has been reported. |
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==Hair loss benefits== |
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Nizoral shampoo has shown to be beneficial in men suffering from [[androgenic alopecia]]. One 1998 study showed that Nizoral 2% worked just as well as [[minoxidil]] 2% (brand name Rogaine) in men with androgenic alopecia. Both medicines increased hair thickness and increased the number of anagen-phase hair follicles on the scalp. Researchers were guarded about the meaning of these results, saying that more rigorous studies on larger groups of men should be done to confirm the findings, both to evaluate the ideal dosage and formulation, and to assess the desirability of routine treatment in this condition.<ref>[http://www.dermadoctor.com/pages/newsletter198.asp Nizoral Shampoo for Hair Loss<!-- Bot generated title -->]</ref> |
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Results so far indicate that both the 1% and 2% dosages have positive hair loss benefits; however the more potent 2% formulation could have better results. Optimal usage is speculated at every third day, leaving the shampoo on the scalp for 3-5 minutes before rinsing. It has been stated that medications capable of maintaining the existing hair population should be regarded as effective treatments for androgenic alopecia. The present data suggests that ketoconazole should enter this group of drugs.<ref>http://www.hairlosstalk.com/download/nizoral.pdf</ref> |
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==References== |
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<div class="references-small"><references /></div> |
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==Brand names== |
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* [[Nizoral]] |
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* [[Xolegel]] |
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== External links == |
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* [http://www.janssenpharmaceutica.be/health_research5_E.asp Janssen Pharmaceutica fungal infections page] |
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* [http://www.doctorfungus.org/thedrugs/Ketoconazole.htm Doctor Fungus ketoconazole page] |
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* [http://www.nizoral.com Nizoral] (manufacturer's website) |
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* [http://ketoconazole.generic-help.com Ketoconazole] (patient information) |
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* [http://ketoconazole.com Ketoconazole] (Up to date product information) |
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* [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12476017 Study comparing the efficacy of ketoconazole (Nizoral) versus zinc pyrithione (Head & Shoulders)] |
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<!--This list needs checking: |
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* dermatophytes |
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* trychophyton |
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* rubrum, T mentagrophytes, T tonsurans, microsporum canis, M. audouni, M. gypseum and Epidermophyton floccosum;yeast: |
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candida albicans,Malassezia, ovale[Pityrosporum orbiculare] also, C. tropicalis as well as the micro-organism responsibly for tinea versicolor, Malassezia furfur [pityrosporum orbiculare]. |
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Presently, the micro-organisms listed above have been proven to be clinically affected. No resistance by the micro-organisms against Ketoconazole is been reported. |
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--> |
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{{Antifungals}} |
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{{Gynecological anti-infectives and antiseptics}} |
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[[Category:Antifungals]] |
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[[Category:Antiandrogens]] |
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[[Category:Imidazoles]] |
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[[Category:Piperazines]] |
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[[de:Ketoconazol]] |
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[[pt:Cetoconazol]] |
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[[ru:Кетоконазол]] |
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[[fi:Ketokonatsoli]] |
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