Terbinafine
Terbinafine. Allylamine antifungal — squalene epoxidase inhibitor blocking ergosterol synthesis upstream of CYP51. Highly lipophilic +… Oral half-life 25 h.
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).
PK: MY TISSUE-ACCUMULATION PRIOR WAS REFUTED AND THE REAL DEFECT IS 3.75x. The stored half-life is verbatim and is the RIGHT ONE: "The apparent terminal half-lives of terbinafine, demethylterbinafine, and the two carboxy metabolites appear to be similar (approximately 25 h)" is the plasma value, and the separate three-week deep-tissue phase is explicitly negligible for exposure — "That terminal elimination phase contributed SO LITTLE TO THE TOTAL EXPOSURE, however, that average concentrations accumulated only approximately two-fold at steady state". No conflation. The defect is class 6: against this record own refs[], a 250 mg dose gives a verbatim "AUC(0.48) of terbinafine was ... 6761.63 +/- 3140.33 ng x h/ml", an observed clearance of 36.97 L/h against the stored 138.6. THERE IS NO HUMAN INTRAVENOUS TERBINAFINE — the only intravenous data is rat and the published human model was fitted to oral data — so every human volume is apparent and dividing by F again is the double division. V 2000 also matched nothing: the verbatim human figure is 11 L/kg and this record own data imply 1334 L. A HARD LIMIT IS RECORDED: no one-compartment model at this half-life can reach the observed peak, which is 8.3x above the best achievable before any choice of volume or rate, because terbinafine has a rapid distribution phase the model has no slot for. ka 0.7 predicted a peak at 4.8 h against a real two. INTERACTIONS: THE DESIPRAMINE EDGE INVERTS THROUGH 3 µM from a verbatim exposure pair, "AUC0-infinity (482 ng.h/ml vs. 2383 ng.h/ml)". The venlafaxine edge is left undeclared because the ratio it would need is not in the visible note, though its stored value sits close enough to the same constant to suggest it belongs to it.
Pharmacokinetics
- Oral — t½ 25 h · F 100% · Vd 1334 L
Related compounds
- Desipramine — warn
- Venlafaxine — warn
Sources: PMID:18751504, PMID:12412819, PMID:17687273, PMID:8573687