Nhg. Holford et al., PHARMACODYNAMICS OF LAZABEMIDE, A REVERSIBLE AND SELECTIVE INHIBITOR OF MONOAMINE-OXIDASE-B, British journal of clinical pharmacology, 37(6), 1994, pp. 553-557
1 The inhibition of monoamine oxidase B (MAO-B) by lazabemide was meas
ured 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 de
fined by a sigmoid I-max-model using either a parametric or semi-param
etric method for predicting plasma drug concentrations. Population par
ameter estimates were obtained by the expectation maximization method
and a standard two-stage method. 3 At the lowest dose platelet MAO-B a
ctivity was almost completely inhibited for around 20 h. No time delay
between plasma drug concentration and resulting inhibition of platele
t 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 laz
abemide (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.