Terbinafine

Category: pharmacological

Aliases: Lamisil

Pharmacological Mechanism

Allylamine antifungal — squalene epoxidase inhibitor blocking ergosterol synthesis upstream of CYP51. Highly lipophilic + keratin-binding → systemic dosing for onychomycosis (~3 month course). Strong CYP2D6 inhibitor (DDI with antidepressants, β-blockers).

Half-Life (t½)

PO: 25h

Dosing Guidelines

PO: Typical 250 mg (Range: 250–250 mg)

Target Organ Systems

digestive
immune-hematologic

Interactions

Desipramine (warn): CYP2D6 inhibition. Madani 2002 (PMID:12412819) verbatim: "significant increase in desipramine C(max) (19 ng/ml vs. 36 ng/ml) and AUC0-infinity (482 ng.h/ml vs. 2383 ng.h/ml)". 12 CYP2D6 EMs (genotyped + phenotyped), terbinafine 250 mg/d × 21d + 50 mg PO desipramine. AUC ratio 2383/482 = 4.94×; Ki ≈ 3/3.94 = 0.761 µM. Long-lasting — C/AUC still elevated 4 wk after terbinafine discontinuation.
Venlafaxine (warn): CYP2D6 inhibition (O-demethylation). Hynninen 2008 (PMID:17687273) verbatim: "During the terbinafine phase, the area under the plasma concentration-time curve (AUC(0-infinity)) of venlafaxine was on average 490% (P<0.001) ... of the corresponding control value". Healthy volunteers, terbinafine pretreatment + 75 mg PO venlafaxine. AUC 4.90×; Ki ≈ 3/3.90 = 0.769 µM. ODV AUC ratio of parent decreased 82% — narrowed therapeutic ratio + serotonergic toxicity risk.

Pathways It Modulates

Fungal ergosterol biosynthesis (inhibitor) — fungal squalene epoxidase
Skin antimicrobial + antiparasitic topicals (inhibitor) — squalene epoxidase (onychomycosis 1st-line)

Chemical Identifiers

PubChem CID: 1549008
Formula: C21H25N
Molecular weight: 291.43 g/mol
InChIKey: DOMXUEMWDBAQBQ-WEVVVXLNSA-N
SMILES: CC(C)(C)C#C/C=C/CN(C)CC1=CC=CC2=CC=CC=C21