Plasma moclobemide and metabolites: lack of correlation with clinical response and biogenic amines

The concentration of the reversible monoamine oxidase type-A (MAO-A) inhibitor moclobemide (Ro 11-1163) was determined by high pressure liquid chromatography (HPLC) in the plasma of 16 depressives treated with moclobemide. Moreover, the inhibitory potency of organic extracts of the plasma on a standard MAO-A preparation from human placenta was measured spectrophotometrically. The inhibitory potency significantly correlated with the HPLC results. However, it overestimated the concentration of moclobemide by one order of magnitude possibly due to the presence of yet unknown metabolites more active than moclobemide itself. These have already been suggested in view of the higher inhibitory potency of moclobemide ex vivo than in vitro. This new methodological approach might represent a comfortable alternative to HPLC procedures in pharmacokinetic studies on reversible MAO inhibitors. Plasma biogenic amines and their metabolites might be indicative of the biologic activity of moclobemide. Plasma homovanillic acid (HVA) decreased and norepinephrine (NE) increased under moclobemide, although insignificantly. There was no significant correlation between the plasma concentration of moclobemide as estimated by either method and the therapeutic response and the change of plasma HVA and NE.