Table 5

Inhibition of terbinafine metabolism

Inhibitor/SubstrateSide-Chain OxidationN-DemethylationDeaminationDihydrodiol FormationTotal Metabolism maximal inhibition
OL+CA+DOL IC50D+DOL+D-DHDs IC50NAL+NM+NA IC50DHDs+D-DHDs IC50
μM %
Analgesic/antipyretic
 Phenacetin, 0–150 μM>150>150>150∼10029
 Phenytoin, 0–200 μM>200>200>200>2004
Antiasthmatic
 Furafylline, 0–100 μM>100>100>100<119
 Ketotifen, 0–200 μM>200>200>200>2001
Antitussive
 Dextromethorphan, 0–150 μM>150>150>150>15023
Antiarrhythmic
 Quinidine, 0–20 μM>20>20>20>2012
Antihypertensive
 Nifedipine, 0–100 μM∼50∼40∼50∼1590
Immunosuppressant
 Cyclosporine A, 0–20 μM>20>20∼12>2030
Antibacterial
 Troleandomycin, 1–100 μM>100>100∼2>10043
 Sulfaphenazole, 0–100 μM∼100∼100∼100>10057
Antifungal
 Ketoconazole, 0–5 μM∼5∼5∼0.3>556
 Clotrimazole, 0–1 μM>1∼1∼0.1>130
 Itraconazole, 0–50 μM>50∼5∼5>5055
 Miconazole, 0–5 μM∼5∼1∼0.5∼572
 Fluconazole, 0–100 μM>100>100∼50>10040
Steroids
 Ethynylestradiol, 0–100 μM∼20∼100>100>10025
Antidiabetic
 Glibornuride, 0–500 μM∼500∼500>500>50023
 Glyburide, 0–100 μM∼50∼50∼505059
 Tolbutamide, 0–500 μM>500>500>500>5005
Skeletal muscle relaxant
 Chlorzoxazone, 0–200 μM>200>200∼100∼10033
Antineoplastic
 Azidothymidine, 0–2000 μM>2000>2000>2000>20006
Other
 Terfenadine, 0–200 μM∼25∼30∼60∼15077
 Disulfiram, 0–500 μM∼10∼15∼25∼2590
 Orphenadrine, 0–600 μM∼300∼300∼300>60056
 (S)-Mephenytoin, 0–240 μM>240>240>240>2406

[14C]Terbinafine (20 μM) metabolism by human liver microsomes (GGM002) in the presence of characteristic and potentially coadministered inhibitors/substrates.