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

Biopharm Drug Dispos. 1995 Nov;16(8):685-94. doi: 10.1002/bdd.2510160807.

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 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / blood
  • Antifungal Agents / pharmacokinetics*
  • Antifungal Agents / urine
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hydrolysis
  • Male
  • Naphthalenes / administration & dosage
  • Naphthalenes / blood
  • Naphthalenes / pharmacokinetics*
  • Naphthalenes / urine
  • Terbinafine

Substances

  • Antifungal Agents
  • Naphthalenes
  • Terbinafine