title: [Pharmacokinetics and metabolism of reversible MAO-A inhibitors in the human].
abstract: Monoamine oxidase (MAO) type A inhibitors are used as antidepressants. A number of drug candidates in this therapeutic class are currently being evaluated clinically. The objective of the present review is to evaluate the pharmacokinetics of five MAO-A inhibitors (moclobemide, toloxatone, brofaromine, cimoxatone, amiflamine). Differences between these drugs exist in their absorption and disposition characteristics. However, a detailed comparison reveals a strong similarity between moclobemide and toloxatone (high hepatic extraction ratio; reduced oral bioavailability due to first-pass metabolism; similar binding to plasma protein, fb approximately 0.23). Elimination half-lives of 1-3 h for moclobemide and toloxatone contrast with the higher values for amiflamine (5-12 h), cimoxatone (9-16 h) and brofaromine (12-15 h). All five MAO-A inhibitors undergo complete hepatic elimination, and only a negligible fraction of the dose (less than 1%) is excreted unchanged in the urine. Oxidation represents the major degradation pathway. Results from studies in populations with increased risk factors are scarce for the discussed MAO-A inhibitors except for moclobemide. For this drug it has been shown that neither age nor reduced kidney function influence plasma levels significantly. Liver insufficiency reduces the body's elimination capacity for moclobemide. As a consequence similar doses result in higher plasma concentrations in liver impaired patients than subjects with normal hepatic function and a dose adjustment may therefore become necessary.
authors.affiliation: Abteilung für Klinische Pharmacologie F. Hoffmann-La Roche & Co. AG, Basel.
authors.forename: M P
authors.initials: MP
authors.lastname: Schoerlin
authors.forename: T W
authors.initials: TW
authors.lastname: Guentert
mesh_terms: D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D001711:Biotransformation; D006801:Humans; D008657:Metabolic Clearance Rate; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship
chemical_list: D000928:Antidepressive Agents; D008996:Monoamine Oxidase Inhibitors
vernacular_title: Pharmakokinetik und Metabolismus reversibler MAO-A-Hemmer beim Menschen.