Detail for Ketoconazole
Basic Information
DrugID 59
DrugName Ketoconazole
DrugDetail Ketoconazole is a synthetic antifungal drug used to prevent and treat fungal skin infections, especially in immunocompromised patients such as those with AIDS or those on chemotherapy. Ketoconazole is sold commercially as an anti-dandruff shampoo, topical cream, and oral tablet. Ketoconazole is very lipophilic, which leads to accumulation in fatty tissues. The less toxic and more effective triazole compounds fluconazole and itraconazole are sometimes preferred for internal use. Ketoconazole is best absorbed at highly acidic levels, so antacids or other causes of decreased stomach acid levels will lower the drug's absorption when taken orally. Absorption can be increased by taking it with an acidic beverage, such as cola.

http://en.wikipedia.org/wiki/Ketoconazole

http://www.drugbank.ca/drugs/DB01026

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

http://www.drugbank.ca/drugs/DB01026

Structure Click to see the orginal picture.
Interaction
Drug Name PMIDLink Reference
Ciclopirox Zarember KA, Cruz AR, Huang CY, Gallin JI. (2009) Antifungal activities of natural and synthetic iron chelators alone and in combination with azole and polyene antibiotics against Aspergillus fumigatus. Antimicrob Agents Chemother. 53(6):2654-6.
Deferiprone Zarember KA, Cruz AR, Huang CY, Gallin JI. (2009) Antifungal activities of natural and synthetic iron chelators alone and in combination with azole and polyene antibiotics against Aspergillus fumigatus. Antimicrob Agents Chemother. 53(6):2654-6.
Ethambutol Cordeiro Rde A, Brilhante RS, Rocha MF, Medrano DJ, Monteiro AJ, Tavares JL, de Lima RA, de Camargo ZP, Sidrim JJ. (2009) In vitro synergistic effects of antituberculous drugs plus antifungals against Coccidioides posadasii. Int J Antimicrob Agents. 34(3):278-80.
Nikkomycin X Hector RF, Schaller K. (1992) Positive interaction of nikkomycins and azoles against Candida albicans in vitro and in vivo. Antimicrob Agents Chemother. 36(6):1284-9.
Nikkomycin Z Hector RF, Schaller K. (1992) Positive interaction of nikkomycins and azoles against Candida albicans in vitro and in vivo. Antimicrob Agents Chemother. 36(6):1284-9.
nitric oxide McElhaney-Feser GE, Raulli RE, Cihlar RL. (1998) Synergy of nitric oxide and azoles against Candida species in vitro. Antimicrob Agents Chemother. 42(9):2342-6.
Amphotericin B Odds F.C. (1982) Interactions among amphotericin-b, 5-fluorocytosine, ketoconazole, and miconazole against pathogenic fungi invitro. Antimicrobial Agents and Chemotherapy 22:763-770.
Beauvericin Zhang L.X., Yan K.Z., Zhang Y., Huang R., Bian J., Zheng C.S., Sun H.X., Chen Z.H., Sun N., An R., Min F.G., Zhao W.B., Zhuo Y., You J.L., Song Y.J., Yu Z.Y., Liu Z.H., Yang K.Q., Gao H., Dai H.Q., Zhang X.L., Wang J., Fu C.Z., Pei G., Liu J.T., Zhang S., Goodfellow M., Jiang Y.Y., Kuai J., Zhou G.C., Chen X.P. (2007) High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections. Proceedings of the National Academy of Sciences of the United States of America 104:4606-4611. DOI: 10.1073/pnas.0609370104.
Berberine Zhang L.X., Yan K.Z., Zhang Y., Huang R., Bian J., Zheng C.S., Sun H.X., Chen Z.H., Sun N., An R., Min F.G., Zhao W.B., Zhuo Y., You J.L., Song Y.J., Yu Z.Y., Liu Z.H., Yang K.Q., Gao H., Dai H.Q., Zhang X.L., Wang J., Fu C.Z., Pei G., Liu J.T., Zhang S., Goodfellow M., Jiang Y.Y., Kuai J., Zhou G.C., Chen X.P. (2007) High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections. Proceedings of the National Academy of Sciences of the United States of America 104:4606-4611. DOI: 10.1073/pnas.0609370104.
Chlorpromazine Bengigi G., Polacheck I., Eilam Y. (1988) In vitro synergistic activity ofwith trifluoperazine and with chlorpromazine against medically important yeasts. Chemotherapy 34:96-100.
Cyclosporine A Zhang L.X., Yan K.Z., Zhang Y., Huang R., Bian J., Zheng C.S., Sun H.X., Chen Z.H., Sun N., An R., Min F.G., Zhao W.B., Zhuo Y., You J.L., Song Y.J., Yu Z.Y., Liu Z.H., Yang K.Q., Gao H., Dai H.Q., Zhang X.L., Wang J., Fu C.Z., Pei G., Liu J.T., Zhang S., Goodfellow M., Jiang Y.Y., Kuai J., Zhou G.C., Chen X.P. (2007) High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections. Proceedings of the National Academy of Sciences of the United States of America 104:4606-4611. DOI: 10.1073/pnas.0609370104.
Disulfiram Borisy A.A., Elliott P.J., Hurst N.W., Lee M.S., Lehar J., Price E.R., Serbedzija G., Zimmermann G.R., Foley M.A., Stockwell B.R., Keith C.T. (2003) Systematic discovery of multicomponent therapeutics. Proceedings of the National Academy of Sciences of the United States of America 100:7977-7982. DOI: 10.1073/pnas.1337088100.
Geldanamycin Zhang L.X., Yan K.Z., Zhang Y., Huang R., Bian J., Zheng C.S., Sun H.X., Chen Z.H., Sun N., An R., Min F.G., Zhao W.B., Zhuo Y., You J.L., Song Y.J., Yu Z.Y., Liu Z.H., Yang K.Q., Gao H., Dai H.Q., Zhang X.L., Wang J., Fu C.Z., Pei G., Liu J.T., Zhang S., Goodfellow M., Jiang Y.Y., Kuai J., Zhou G.C., Chen X.P. (2007) High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections. Proceedings of the National Academy of Sciences of the United States of America 104:4606-4611. DOI: 10.1073/pnas.0609370104.
Lovastatin Zhang L.X., Yan K.Z., Zhang Y., Huang R., Bian J., Zheng C.S., Sun H.X., Chen Z.H., Sun N., An R., Min F.G., Zhao W.B., Zhuo Y., You J.L., Song Y.J., Yu Z.Y., Liu Z.H., Yang K.Q., Gao H., Dai H.Q., Zhang X.L., Wang J., Fu C.Z., Pei G., Liu J.T., Zhang S., Goodfellow M., Jiang Y.Y., Kuai J., Zhou G.C., Chen X.P. (2007) High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections. Proceedings of the National Academy of Sciences of the United States of America 104:4606-4611. DOI: 10.1073/pnas.0609370104.
Pentamidine Borisy A.A., Elliott P.J., Hurst N.W., Lee M.S., Lehar J., Price E.R., Serbedzija G., Zimmermann G.R., Foley M.A., Stockwell B.R., Keith C.T. (2003) Systematic discovery of multicomponent therapeutics. Proceedings of the National Academy of Sciences of the United States of America 100:7977-7982. DOI: 10.1073/pnas.1337088100.
Radicicol Zhang L.X., Yan K.Z., Zhang Y., Huang R., Bian J., Zheng C.S., Sun H.X., Chen Z.H., Sun N., An R., Min F.G., Zhao W.B., Zhuo Y., You J.L., Song Y.J., Yu Z.Y., Liu Z.H., Yang K.Q., Gao H., Dai H.Q., Zhang X.L., Wang J., Fu C.Z., Pei G., Liu J.T., Zhang S., Goodfellow M., Jiang Y.Y., Kuai J., Zhou G.C., Chen X.P. (2007) High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections. Proceedings of the National Academy of Sciences of the United States of America 104:4606-4611. DOI: 10.1073/pnas.0609370104.
Retigeric acid B Sun L.M., Sun S.J., Cheng A.X., Wu X.Z., Zhang Y., Lou H.X. (2009) In Vitro Activities of Retigeric Acid B Alone and in Combination with Azole Antifungal Agents against Candida albicans. Antimicrobial Agents and Chemotherapy 53:1586-1591. DOI: 10.1128/aac.00940-08.
Ribavirin Borisy A.A., Elliott P.J., Hurst N.W., Lee M.S., Lehar J., Price E.R., Serbedzija G., Zimmermann G.R., Foley M.A., Stockwell B.R., Keith C.T. (2003) Systematic discovery of multicomponent therapeutics. Proceedings of the National Academy of Sciences of the United States of America 100:7977-7982. DOI: 10.1073/pnas.1337088100.
Terbinafine Meletiadis J., Mouton J.W., Meis J., Verweij P.E. (2003) In vitro drug interaction modeling of combinations of azoles with terbinafine against clinical Scedospotium prolificans isolates. Antimicrobial Agents and Chemotherapy 47:106-117. DOI: 10.1128/aac.47.1.106-117.2003.
Target
TargetName References EssentialGene? Link
(R)-limonene 6-monooxygenase No
21-OHase No
Albendazole monooxygenase No
Aromatase Yes
ATP-binding cassette sub-family B member 1 No
CYPIA1 No
CYPIA2 Yes
CYPIIB6 No
CYPIIC11 No
CYPIIC8 No
CYPIID6 No
CYPIIIA5 No
CYPIIIA7 No
CYPIVA10 No
CYPIVF2 No
CYPXIB1 No
CYPXVII Yes
Cytochrome P450 1B1 No
Cytochrome P450 26A1 Yes
Cytochrome P450 2A6 No
Cytochrome P450 2B1 No
Cytochrome P450 2F1 No
Heme oxygenase 1 Yes
Heme oxygenase 2 No
Lanosterol 14-alpha demethylase No
Cytochrome P450 51 No
sterol 14alpha-demethylase ihibitor No
PathWay
PathWay Name Path Picture
Steroid biosynthesis - Reference pathway (KO)