Kinetics and metabolism of nomifensine.
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.
D000818:Animals; D001345:Autoradiography; D055598:Chemical Phenomena; D002621:Chemistry; D005965:Glucuronates / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism*; D007700:Kinetics; D009627:Nomifensine / Q000097:blood / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution
D005965:Glucuronates; D007546:Isoquinolines; D009627:Nomifensine