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Pharmacokinetics of terbinafine and of its five main metabolites in plasma and urine, following a single oral dose in healthy subjects

1995; Wiley; Volume: 16; Issue: 8 Linguagem: Inglês

10.1002/bdd.2510160807

1099-081X

Henri Humbert, M. D. Cabiac, J. Denouël, Stéphane Kirkesseli,

Antifungal resistance and susceptibility

Abstract The plasma pharmacokinetics, and the urinary excretion, of terbinafine and its five main metabolites have been investigated after a single oral dose administration of 125 mg to 16 healthy subjects. In plasma, the highest concentrations are observed for the two carboxybutyl metabolites, with a predominance for the carboxybutylterbinafine. For this metabolite, as compared to terbinafine, the C max and AUC are 2.4 and 13 times higher respectively. The demethylterbinafine presents a plasma profile close to that of terbinafine. The two hydroxy metabolites are only found as glucuronide and are of minor importance. The apparent terminal half‐lives of terbinafine, demethylterbinafine, and the two carboxy metabolites appear to be similar (∼ 25h). As compared to the plasma concentration of total radioactivity observed after a single oral administration of the same dose of 14 C‐terbinafine, the parent drug and these five metabolites, account for more than 80% of the total radioactivity in plasma over the 0–48 h interval following administration. In urine, the major metabolite is demethylcarboxybutylterbinafine, which amounted to about 10% of the administered dose. Terbinafine and demethylterbinafine are only excreted as trace amounts in urine. Carboxybutylterbinafine and the two hydroxy metabolites are excreted in the range of 0.5–2% either as glucuronides or free. Urinary excretion over the 0–48h interval of terbinafine and of the five metabolites amounted to about 14% of the administered dose. This is far below the level of total radioactivity measured in urine over the same interval (∼ 57%), after administration of 14 C‐terbinafine. This shows in contrast to plasma, that numerous other metabolites are present in urine.