{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:52:09Z","timestamp":1783075929974,"version":"3.54.6"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,10,15]],"date-time":"2008-10-15T00:00:00Z","timestamp":1224028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:sec><jats:label\/><jats:p> <jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003Moclobemide (MCB) undergoes extensive both presystemic and systemic metabolism that can be affected by concomitant drugs.<\/jats:p><jats:p>\u2022\u2003Valproic acid (VPA) and carbamazepine (CBZ) have been found to interact with psychotropic medications of all classes and many other drugs; VPA acts as a broad\u2010spectrum inhibitor, and CBZ as a potent inducer of a variety of drug\u2010metabolizing enzymes.<\/jats:p><jats:p>\u2022\u2003There have been no previous studies designed to investigate a potential pharmacokinetic (PK) interaction between MCB and VPA or CBZ; however, these agents are likely to be used concomitantly for the treatment of depressive disorders.<\/jats:p><jats:p> <jats:bold>WHAT THIS STUDY ADDS<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003VPA does not significantly affect PK or metabolism of MCB at steady state.<\/jats:p><jats:p>\u2022\u2003CBZ significantly decreases MCB exposure. This effect is time\u2010dependent, being more pronounced after 3\u20135 weeks of co\u2010administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>AIM<\/jats:title><jats:p>To assess the impact of valproic acid (VPA) and carbamazepine (CBZ) on moclobemide (MCB) pharmacokinetics (PK) and metabolism at steady state in depressive patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Twenty\u2010one inpatients with recurrent endogenous depression received MCB (150\u2003mg t.i.d.), either as monotherapy or in combination with VPA (500\u2003mg b.i.d.) or CBZ (200\u2003mg b.i.d.) in a nonrandomized manner. Steady\u2010state plasma PK parameters of MCB and its two metabolites, Ro 12\u20108095 and Ro 12\u20105637, were derived. Clinical assessments of treatment efficacy were performed weekly using standard depression rating scales.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>CBZ, but not VPA, was associated with decreases in the MCB AUC by 35% [from 7.794 to 5.038\u2003mg\u2003h\u2003l<jats:sup>\u22121<\/jats:sup>; 95% confidence interval (CI) \u22124.84863, \u22120.66194; <jats:italic>P<\/jats:italic>\u2003=\u20030.01] and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> by 28% (from 1.911 to 1.383\u2003mg l<jats:sup>\u22121<\/jats:sup>; 95% CI \u22120.98197, \u22120.07518; <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05), and an increase in its oral clearance by 41% (from 0.323 to 0.454\u2003l h<jats:sup>\u22121<\/jats:sup>\u2003kg<jats:sup>\u22121<\/jats:sup>; 95% CI 0.00086, 0.26171; <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05) after 4 weeks of co\u2010administration. MCB through concentrations were also decreased, on average by 41% (from 0.950 to 0.559\u2003mg l<jats:sup>\u22121<\/jats:sup>; 95% CI \u22120.77479, \u22120.03301; <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05). However, the efficacy in this group of patients was not inferior to the controls, for several possible reasons. Overall tolerability of all study medications was good.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>VPA does not significantly affect PK or metabolism of MCB, whereas CBZ time\u2010dependently decreases MCB exposure, probably by inducing metabolism of MCB and its major plasma metabolite. The actual clinical relevance of the observed MCB\u2013CBZ PK interaction needs to be further evaluated in a more comprehensive study.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2008.03326.x","type":"journal-article","created":{"date-parts":[[2008,10,15]],"date-time":"2008-10-15T12:35:44Z","timestamp":1224074144000},"page":"199-208","source":"Crossref","is-referenced-by-count":12,"title":["Moclobemide monotherapy <i>vs.<\/i> combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study"],"prefix":"10.1111","volume":"67","author":[{"given":"Anita","family":"Rakic 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