Ketoconazole

• CAT Number: A000489
• CAS Number: 65277-42-1
• Molecular Formula: C26H28Cl2N4O4
• Molecular Weight: 531.4
• Purity: ≥95%
• Target: P450
• Solubility: >23.4mg/mL in DMSO
• Storage: -20°C
• IUPAC Name: 1-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone
• InChI: InChI=1S/C26H28Cl2N4O4/c1-19(33)31-10-12-32(13-11-31)21-3-5-22(6-4-21)34-15-23-16-35-26(36-23,17-30-9-8-29-18-30)24-7-2-20(27)14-25(24)28/h2-9,14,18,23H,10-13,15-17H2,1H3/t23-,26-/m0/s1
• InChIKey: XMAYWYJOQHXEEK-OZXSUGGESA-N
• SMILES: CC(=O)N1CCN(CC1)C2=CC=C(C=C2)OCC3COC(O3)(CN4C=CN=C4)C5=C(C=C(C=C5)Cl)Cl

Ketoconazole (CAS 65277-42-1) is a synthetic imidazole antifungal drug used primarily to treat fungal infections. It is sold commercially as a tablet for oral administration (although this use has been discontinued in a number of countries), and in a variety of formulations for topical administration, such as creams (used to treat tinea; cutaneous candidiasis, including candidal paronychia; and pityriasis versicolor) and shampoos (used primarily to treat dandruff—seborrhoeic dermatitis of the scalp).

Overview of Clinical Research

Ketoconazole is a 14-alpha demethylase inhibitor. It is marketed to treat Seborrhoeic dermatitis.

Reference

1: Viljoen JM, Botes D, Steenekamp JH. Formulation and evaluation of selected transmucosal dosage forms containing a double fixed-dose of acyclovir and ketoconazole. Eur J Pharm Sci. 2017 Nov 1;111:503-513. doi: 10.1016/j.ejps.2017.10.033. [Epub ahead of print] PubMed PMID: 29080856.
2: Kusawake T, den Adel M, Groenendaal-van de Meent D, Garcia-Hernandez A, Takada A, Kato K, Ohtsu Y, Katashima M. Pharmacokinetic Evaluation of the Interactions of Amenamevir (ASP2151) with Ketoconazole, Rifampicin, Midazolam, and Warfarin in Healthy Adults. Adv Ther. 2017 Oct 26. doi: 10.1007/s12325-017-0634-4. [Epub ahead of print] PubMed PMID: 29076107.
3: Nguyen D, Mizne S. Effects of Ketoconazole on the Pharmacokinetics of Mifepristone, a Competitive Glucocorticoid Receptor Antagonist, in Healthy Men. Adv Ther. 2017 Oct;34(10):2371-2385. doi: 10.1007/s12325-017-0621-9. Epub 2017 Oct 11. PubMed PMID: 29022184; PubMed Central PMCID: PMC5656713.
4: Tsume Y, Igawa N, Drelich AJ, Amidon GE, Amidon GL. The Combination of GIS and Biphasic to Better Predict In Vivo Dissolution of BCS Class IIb Drugs, Ketoconazole and Raloxifene. J Pharm Sci. 2017 Sep 15. pii: S0022-3549(17)30622-6. doi: 10.1016/j.xphs.2017.09.002. [Epub ahead of print] PubMed PMID: 28919384.
5: Sharma N, Singhal D, Maharana PK, Sinha R, Agarwal T, Upadhyay AD, Velpandian T, Satpathy G, Titiyal JS. Comparison of Oral Voriconazole Versus Oral Ketoconazole as an Adjunct to Topical Natamycin in Severe Fungal Keratitis: A Randomized Controlled Trial. Cornea. 2017 Dec;36(12):1521-1527. doi: 10.1097/ICO.0000000000001365. PubMed PMID: 28902012.
6: Sung HJ, Yoon IH, Kim JH. Putative contact ketoconazole shampoo-triggered pemphigus foliaceus in a dog. Can Vet J. 2017 Sep;58(9):914-918. PubMed PMID: 28878412; PubMed Central PMCID: PMC5556470.
7: Zhu M, Wang J, Li N. A novel thermo-sensitive hydrogel-based on poly(N-isopropylacrylamide)/hyaluronic acid of ketoconazole for ophthalmic delivery. Artif Cells Nanomed Biotechnol. 2017 Aug 21:1-6. doi: 10.1080/21691401.2017.1368024. [Epub ahead of print] PubMed PMID: 28826241.
8: Liu J, Cai Y, Lu G, Dan X, Wu D, Yan Z. Interaction of erythromycin and ketoconazole on the neurological, biochemical and behavioral responses in crucian carp. Environ Toxicol Pharmacol. 2017 Oct;55:14-19. doi: 10.1016/j.etap.2017.08.002. Epub 2017 Aug 7. PubMed PMID: 28802958.
9: Pathak SM, Ruff A, Kostewicz ES, Patel N, Turner DB, Jamei M. Model-Based Analysis of Biopharmaceutic Experiments To Improve Mechanistic Oral Absorption Modeling: An Integrated in Vitro in Vivo Extrapolation Perspective Using Ketoconazole as a Model Drug. Mol Pharm. 2017 Aug 25. doi: 10.1021/acs.molpharmaceut.7b00406. [Epub ahead of print] PubMed PMID: 28771009.
10: Nunes DCO, Bispo-da-Silva LB, Napolitano DR, Costa MS, Figueira MMNR, Rodrigues RS, Rodrigues VM, Yoneyama KAG. In vitro additive interaction between ketoconazole and antimony against intramacrophage Leishmania (Leishmania) amazonensis amastigotes. PLoS One. 2017 Jun 29;12(6):e0180530. doi: 10.1371/journal.pone.0180530. eCollection 2017. PubMed PMID: 28662149; PubMed Central PMCID: PMC5491259.