Clinical pharmacokinetics of the monoamine oxidase-A inhibitor moclobemide

Michael Mayersohn, T. W. Guentert

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

There has been a resurgence of interest in the use of monoamine oxidase (MAO) enzyme inhibitors for the treatment of depression. Unlike the first-generation MAO inhibitors, the current drugs are readily reversible in their action, resulting in far less concern about interactions with certain foods and drugs which could lead to serious presser effects. Furthermore, the current drugs are Ear more selective in their actions as a result of the ability to affect either the MAO-A or the MAO-B isoenzyme. Moclobemide is an example of a reversible MAO-A inhibitor which has been extensively studied and whose pharmacokinetic, clinical pharmacological and toxicological profiles have been thoroughly defined. Moclobemide has a short disposition half-life and intermediate values for systemic clearance and volume of distribution; half-life increases somewhat with dose. The drug is completely metabolised by the liver. Moclobemide is rapidly and completely absorbed following oral administration in a variety of dosages and forms. The drug has a high intrinsic (apparent oral) clearance which results in a substantial hepatic first-pass effect and, while there is marked interindividual variation, differences within an individual are small. A time- and dose-dependence is observed with multiple oral administration: clearance decreases with administration during the first week and thereafter remains constant. The exact mechanism of this effect is not known, but it may reflect inhibition of elimination by metabolites (the kinetics may always be described as being first-order). Moclobemide disposition is not affected by renal disease, nor is there substantial alteration with advanced age. Liver disease causes a dramatic reduction in clearance; dosage must be adjusted for patients with liver disease. There is minimal transfer of the drug into breast milk, such that breast-feeding neonates are exposed to only a very small dose of the drug. Moclobemide administration results in a minimal interaction with exogenous amines (e.g. tyramine and presser amine drugs); the so-called 'cheese effect' is therefore of little concern. As a result, the drug has an excellent tolerability profile both within the therapeutic dose range and in overdose (no deaths have been attributed to moclobemide intoxication per se). Cimetidine inhibits the elimination of moclobemide. Moclobemide appears to affect several isoenzymes of the cytochrome P450 (CYP) system (CYP2C19, CYP2D6 and CYP1A2). The adverse events profile of moclobemide indicates only mild and transient effects at a relatively low rate of occurrence.

Original languageEnglish (US)
Pages (from-to)292-332
Number of pages41
JournalClinical Pharmacokinetics
Volume29
Issue number5
StatePublished - 1995

Fingerprint

Moclobemide
Monoamine Oxidase Inhibitors
Monoamine Oxidase
Pharmacokinetics
Pharmaceutical Preparations
Isoenzymes
Amines
Oral Administration
Half-Life
Liver Diseases
Cytochrome P-450 CYP1A2
Cytochrome P-450 CYP2D6
Tyramine
Aptitude
Liver
Cimetidine
Dosage Forms
Cheese
Enzyme Inhibitors
Human Milk

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Clinical pharmacokinetics of the monoamine oxidase-A inhibitor moclobemide. / Mayersohn, Michael; Guentert, T. W.

In: Clinical Pharmacokinetics, Vol. 29, No. 5, 1995, p. 292-332.

Research output: Contribution to journalArticle

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