Inhibition of fluvastatin metabolism
| Inhibitor/Substrate | Inhibition of 6-OH + N-deisopropyl IC50 | Inhibition of 5-OH IC50 | Inhibitor/Substrate | Inhibition of 6-OH + N-deisopropyl IC50 | Inhibition of 5-OH IC50 |
|---|---|---|---|---|---|
| μM | μM | μM | μM | ||
| Analgesic/antipyretic: | Steroids: | ||||
| Diclofenac | ∼3 | 20 | Ethinyl estradiol | ∼3 | ∼5 |
| Phenacetin | >100 | >100 | Antitussive: | ||
| Sulfinpyrazone | ∼100 | >100 | Dextromethorphan | >100 | ∼100 |
| Antihypertensive: | Antiarrhythmic: | ||||
| Nifedipine | 2.5 | 7 | Quinidine | >100 | >100 |
| Mibefradila | 60 | 1 | Sparteine | >100 | >100 |
| Isradipineb | 4 | 4 | Antihypercholesterolemic: | ||
| Valsartan | >100 | >100 | Lovastatin | ∼7 | ∼5 |
| Immunosuppressant: | Pravastatinb | >100 | >100 | ||
| Cyclosporine A | ∼20 | ∼20 | Clofibrate | 10 | 9 |
| Antibiotic: | Anticoagulant: | ||||
| Erythromycin | ∼90 | ∼70 | Warfarin | 8 | 9 |
| Antidiabetic: | Skeletal muscle relaxant: | ||||
| Chlorpropamide | >100 | >100 | Chlorzoxazone | ∼100 | >100 |
| Glyburide | ∼5 | ∼9 | Anti Asthmatic: | ||
| Tolbutamide | >1000 | >1000 | Furafylline | >100 | >100 |
| Antifungal: | Antibacterial: | ||||
| Ketoconazole | 90 | 8 | Sulfaphenazole | ∼0.25 | >100 |
| Itraconazolea | >100 | >100 | Troleandomycin | >100 | ∼100 |
| Terbinafineb | >100 | >100 | |||
| Antineoplastic: | |||||
| Paclitaxel | 8 | 10 |
[14C]Fluvastatin (0.6 μM) metabolism by human liver microsomes (M8) was determined in the presence of various concentrations of characteristic inhibitors/substrates and potentially coadministered compounds. Inhibitory concentrations (IC50) were determined as described in Materials and Methods.
Additional human livers used were: a M8 + HL44 + HL46, b M8 + HL44