PHARMACODYNAMICS OF LAZABEMIDE, A REVERSIBLE AND SELECTIVE INHIBITOR OF MONOAMINE-OXIDASE-B

1 The inhibition of monoamine oxidase B (MAO-B) by lazabemide was measured in platelets collected from 35 young (19-36 years) and 40 older (60-78 years) healthy volunteers after single (100-300 mg) and multiple (100-350 mg twice daily) oral doses respectively. 2 The relationship of the effect with plasma concentrations of the MAO-B inhibitor was defined by a sigmoid I-max-model using either a parametric or semi-parametric method for predicting plasma drug concentrations. Population parameter estimates were obtained by the expectation maximization method and a standard two-stage method. 3 At the lowest dose platelet MAO-B activity was almost completely inhibited for around 20 h. No time delay between plasma drug concentration and resulting inhibition of platelet MAO-B occurred. Low concentrations of the inhibitor produced 50% of maximum inhibition (IC50, estimates for population mean +/- s.d.: 0.48 +/- 0.89 mu g 1(-1) for young and 1.5 +/- 2.3 mu g 1(-1) for elderly subjects). The maximum extent of enzyme inhibition attributable to lazabemide (I-max) was 94 +/- 5.1% and 96 +/- 4.5% in the young and older populations. There was no correlation between age and either I-max or IC50.