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Pharmacodynamics of lazabemide, a reversible and selective inhibitor of monoamine oxidase B.
Author(s) -
Holford NH,
Guentert TW,
Dingemanse J,
Kettler R
Publication year - 1994
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1994.tb04303.x
Subject(s) - ic50 , monoamine oxidase , population , pharmacodynamics , chemistry , pharmacokinetics , platelet , monoamine oxidase b , pharmacology , endocrinology , medicine , enzyme , biochemistry , in vitro , environmental health
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 Imax‐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 microgram l‐1 for young and 1.5 +/‐ 2.3 micrograms l‐1 for elderly subjects). The maximum extent of enzyme inhibition attributable to lazabemide (Imax) was 94 +/‐ 5.1% and 96 +/‐ 4.5% in the young and older populations. There was no correlation between age and either Imax or IC50. 4. Model parameters describing the interaction of lazabemide with the enzyme did not change over the treatment period of 7 days.