Kinetics and metabolism of nomifensine

J Clin Psychiatry. 1984 Apr;45(4 Pt 2):21-5.

Abstract

Metabolic and pharmacokinetic studies of nomifensine maleate, a tetrahydroisoquinoline derivative with antidepressant properties, are reviewed. Results of pharmacokinetic studies indicate that nomifensine has a short distribution phase and a large volume of distribution. It is rapidly metabolized to its N-glucuronide. Plasma levels of nomifensine-N-glucuronide are up to 100-fold higher than those of nomifensine, obviously because of a smaller volume of distribution. As nomifensine-N-glucuronide is extremely unstable and cleaved to nomifensine, determinations of nomifensine are easily falsified. It is therefore recommended only to determine the sum of nomifensine and its N-glucuronide (total nomifensine) in clinical trials. Kinetics of total nomifensine can best be described by the open two-compartment model: Maximum plasma levels are obtained 1-2 hours postadministration; mean elimination half-life is 2 hours. Excretion is almost entirely by the kidneys, with approximately 88% of an oral dose excreted within 24 hours.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoradiography
  • Chemical Phenomena
  • Chemistry
  • Glucuronates / metabolism
  • Half-Life
  • Humans
  • Isoquinolines / metabolism*
  • Kinetics
  • Nomifensine / blood
  • Nomifensine / metabolism*
  • Rats
  • Tissue Distribution

Substances

  • Glucuronates
  • Isoquinolines
  • Nomifensine