Pharmacokinetics of and monoamine oxidase B inhibition by (E)-4-fluoro-beta-fluoromethylene benzene butanamine in man.

MDL 72974A ((E)-4-fluoro-beta-fluoromethylene benzene butanamine HCl salt, CAS 120635-25-8) is a new irreversible inhibitor of the B form of monoamine oxidase (MAO-B). MDL 72974A's pharmacokinetic parameters were evaluated after administration of a single oral dose and after multiple oral doses. The concentration of parent drug was determined in plasma using a solid-liquid extraction method and gas chromatographic-mass spectrometric analysis. MDL 72974A produced significant inhibition of platelet MAO-B activity at all of the doses > or = 0.5 mg (> 95% after 1 h). The pharmacokinetic parameters showed a short plasma half-life (1 h) and a high total body clearance (Cltot) both probably due to extensive and rapid metabolism as suggested by the low urinary excretion of unchanged drug (< 1% of the administered dose). After the administration of multiple doses of MDL 72974A, a decrease in Cltot and a concomitant increase in the AUC and t1/2, was observed, probably due to a change in the elimination rate of MDL 72974A. Due to the once-a-day dosing schedule and the short plasma t1/2, no drug accumulation occurred.