product name Ketoconazole
Description: Ketoconazole is a synthetic imidazole antifungal drug used primarily to treat fungal infections. Ketoconazole inhibits cyclosporine oxidase and testosterone 6 beta-hydroxylase with IC50 of 0.19 mM and 0.22 mM, respectively. It is sold commercially as a tablet for oral administration, 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).
References: Drug Alcohol Depend. 1998 Dec 1;53(1):67-77.; Horm Metab Res. 1992 Aug;24(8):367-70.
531.43
Formula
C26H28Cl2N4O4
CAS No.
65277-42-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 7 mg/mL (13.2 mM)
Water: <1 mg/mL
Ethanol: 5 mg/mL (9.4 mM)
Solubility (In vivo)
30% propylene glycol, 5% Tween 80, 65% D5W: 30mg/mL
Synonyms
Nizoral, Kuric, Fungoral, Ketoderm
other peoduct :
| In Vitro |
In vitro activity: Ketoconazole interacts with androgen receptors in a competitive fashion in intact human foreskin fibroblasts. Ketoconazole competes for [3H]dexamethasone binding to fibroblast glucocorticoid receptors with IC50 of 0.3 mM. Ketoconazole reduces cell proliferation and [3H]thymidine incorporation with IC50 of 2.5 mM in the serum independent HT29-S-B6 colon cell clone. Ketoconazole inhibits the incorporation of [3H]thymidine with IC50 of 2 μM and 13 μM in the Evsa-T cell line and MDA-MB-231 cell line, respectively. Ketoconazole induces a decrease of the number of cells in S phase and a corresponding increase of the percentage of cells in Go-G1 in HT29-S-B6 cells. Ketoconazole is susceptable to several Malassezia species with minimum inhibitory concentrations (MICs) of 0.03 µg/mL. Kinase Assay: Fibroblasts are grown to confluence in five or six 150 cm2 tissue culture flasks for routine assay. This usually requires 4-6 weeks from the time of the initial seeding of the cell line. All studies are performed between passages 3-20. Two days before assay, the medium is changed to one lacking fetal calf serum. This is repeated again 24 hours before assay. Competition assays are performed with 0.5-1.0 nM [3H]R1881 and increasing amounts of the nonradioactive compounds. Binding to low affinity sites is determined in the presence of 5 × 10-7 M R1881 and is subtracted from whole cell binding of [3H]R 1881 obtained in the absence of any inhibitor to assess binding to 5 high affinity site. Cell Assay: HT29-S-B6 cells (5×105) are plated in 35-mm Petri dishes. The next day, the medium is changed and effectors are added in a small volume (10-20 μL). The incubation medium is renewed every day during the experiments. The same triplicate dishes are used for cell counts, [3H]thymidine incorporation, and flow cytometry. [3H]Thymidine (0.5 μCi) is allowed to incorporate for 24 hours; at the end of incubation, cells are rinsed with 1 mL of medium, detached with 1 mL of trypsin-EDTA, and diluted (1:3) with the culture medium. An aliquot (0.5-1 mL) is used for cell count with a Coulter Counter. |
|---|---|
| In Vivo | Ketoconazole (25 mg/kg, i.p.) significantly decreases plasma corticosterone and reduces low dose cocaine self-administration without affecting food-reinforced responding in rats. Ketoconazole raises the AUC of orally administered digoxin from 63 mg x h/L to 411 mg x h/L in rats. Ketoconazole raises the AUC of intravenously administered digoxin from 93 mg × h/L to 486 mg × h/L in rats. Ketoconazole increases digoxin bioavailability from 0.68 to 0.84 in rats, while mean absorption time is reduced from 1.1 hours to 0.3 hour. |
| Animal model | Male Wistar rats |
| Formulation & Dosage | Dissolved in 0saline; 25 mg/kg; i.p. injection |
| References | Drug Alcohol Depend. 1998 Dec 1;53(1):67-77.; Horm Metab Res. 1992 Aug;24(8):367-70. |
