Ketoconazole (R-41400), a CYP3A4 inhibitor, is an imidazole anti-fungal agent.

Testosterone 6β-hydroxylase:0.22 mM, Cyclosporine oxidase:0.19 mM

腹腔注射Ketoconazole（25 mg/kg）后,大鼠体内血浆皮质酮浓度明显降低,也可使低剂量可卡因自我给药减少.Ketoconazole处理组大鼠,地高辛生物有效性得到提高,从0.68提高至0.84 ,而平均吸收时间从1.1 h减少至0.3 h.此外,地高辛的口服AUC值也得到提高,从63 mg·h/L提高至411 mg·h/L.地高辛的静脉注射AUC值也被提高,从93 mg·h/L提高至486 mg·h/L.

在HT29-S-B6结肠癌细胞中,Ketoconazole剂量依赖性地降低细胞增殖,[3H]胸苷渗透,IC50为2.5 mM。在Evsa-T细胞系和MDA-MB-231 细胞系中,Ketoconazole抑制[3H]胸苷渗透,IC50 分别为2 μM 和13 μM。在HT29-S-B6细胞中,Ketoconazole在24 h内,剂量依赖性地诱导S期细胞数减少（从17%降低至3%）,Go-G1期细胞百分数则相应增加（从64% 增加至80%）。通过与[3H]Dexamethasone竞争性结合的方式,Ketoconazole能够抑制成纤维细胞糖皮质激素受体,IC50为0.3 mM。几种马拉色霉菌种对Ketoconazole较为敏感,最小抑制浓度为0.03 μg/mL。

Whole Cell [3H]R1881 Binding 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

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.(Only for Reference)