Kinetics and metabolism of nomifensine
by
Heptner W, Hornke I, Uihlein M
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.

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