PHARMACOKINETICS OF TERBINAFINE AND OF ITS 5 MAIN METABOLITES IN PLASMA AND URINE, FOLLOWING A SINGLE ORAL DOSE IN HEALTHY-SUBJECTS

The plasma pharmacokinetics, and the urinary excretion, of terbinafine and its five main metabolites have been investigated after a single o ral dose administration of 125 mg to 16 healthy subjects. In plasma, t he highest concentrations are observed for the two carboxybutyl metabo lites, with a predominance for the carboxybutylterbinafine. For this m etabolite, as compared to terbinafine, the C-max and AUC are 2.4 and 1 3 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 t erminal half-lives of terbinafine, demethylterbinafine, and the two ca rboxy metabolites appear to be similar (similar to 25 h). As compared to the plasma concentration of total radioactivity observed after a si ngle oral administration of the same dose of C-14-terbinafine, the par ent drug and these five metabolites, account for more than 80% of the total radioactivity in plasma over the 0-48 h interval following admin istration. In urine, the major metabolite is demethylcarboxybutylterbi nafine, which amounted to about 10% of the administered dose. Terbinaf ine and demethylterbinafine are only excreted as trace amounts in urin e. Carboxybutylterbinafine and the two hydroxy metabolites are excrete d in the range of 0.5-2% either as glucuronides or free. Urinary excre tion over the 0-48 h interval of terbinafine and of the five metabolit es amounted to about 14% of the administered dose. This is far below t he level of total radioactivity measured in urine over the same interv al (similar to 57%), after administration of C-14-terbinafine. This sh ows in contrast to plasma, that numerous other metabolites are present in urine.