Pharmacokinetics of terbinafine and of its five 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 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 Cmax 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 (approximately 25 h). As compared to the plasma concentration of total radioactivity observed after a single oral administration of the same dose of 14C-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 0-48 h 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 (approximately 57%), after administration of 14C-terbinafine. This shows in contrast to plasma, that numerous other metabolites are present in urine.
Humbert
H
H
Sandoz Laboratories, Department of Human Pharmacology, Rueil-Malmaison, France.
Cabiac
M D
MD
Denouël
J
J
Kirkesseli
S
S
D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006868:Hydrolysis; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000077291:Terbinafine
D000935:Antifungal Agents; D009281:Naphthalenes; D000077291:Terbinafine