Terbinafine (DB00857): A Comprehensive Pharmacological and Clinical Monograph

1.0 Executive Summary

Terbinafine is a synthetic allylamine antifungal agent that represents a significant therapeutic advance in the management of superficial dermatophyte infections. As a small molecule drug, it is distinguished by its primarily fungicidal mechanism of action, which contrasts with the fungistatic properties of many older antifungal classes. The primary therapeutic target of Terbinafine is the fungal enzyme squalene epoxidase, a critical component of the ergosterol biosynthesis pathway. Inhibition of this enzyme leads to a dual-pronged assault on the fungal cell: depletion of the essential membrane component ergosterol and the toxic intracellular accumulation of squalene, resulting in cell death. This mechanism is highly selective for the fungal enzyme, affording the drug a wide therapeutic index with respect to human cholesterol synthesis.

Pharmacokinetically, Terbinafine is characterized by its high lipophilicity and keratophilicity. Following oral administration, it is well-absorbed but undergoes significant first-pass metabolism, resulting in approximately 40% bioavailability. Its defining feature is its extensive distribution and accumulation in deep tissue compartments, including the skin, adipose tissue, and, most critically, the nail plate. This sequestration leads to a complex, multiphasic elimination profile with a long terminal half-life of 200-400 hours. This property creates a persistent drug reservoir in target tissues, allowing for high cure rates and low relapse rates in onychomycosis, even after therapy is discontinued.