Article date: February 2009
By: Anita Rakic Ignjatovic, Branislava Miljkovic, Dejan Todorovic, Ivana Timotijevic, Milena Pokrajac, in Volume 67, Issue 2, pages 199-208
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
AIM
To assess the impact of valproic acid (VPA) and carbamazepine (CBZ) on moclobemide (MCB) pharmacokinetics (PK) and metabolism at steady state in depressive patients.
METHODS
Twenty‐one inpatients with recurrent endogenous depression received MCB (150 mg t.i.d.), either as monotherapy or in combination with VPA (500 mg b.i.d.) or CBZ (200 mg b.i.d.) in a nonrandomized manner. Steady‐state plasma PK parameters of MCB and its two metabolites, Ro 12‐8095 and Ro 12‐5637, were derived. Clinical assessments of treatment efficacy were performed weekly using standard depression rating scales.
RESULTS
CBZ, but not VPA, was associated with decreases in the MCB AUC by 35% [from 7.794 to 5.038 mg h l−1; 95% confidence interval (CI) −4.84863, −0.66194; P = 0.01] and Cmax by 28% (from 1.911 to 1.383 mg l−1; 95% CI −0.98197, −0.07518; P < 0.05), and an increase in its oral clearance by 41% (from 0.323 to 0.454 l h−1 kg−1; 95% CI 0.00086, 0.26171; P < 0.05) after 4 weeks of co‐administration. MCB through concentrations were also decreased, on average by 41% (from 0.950 to 0.559 mg l−1; 95% CI −0.77479, −0.03301; P < 0.05). 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.
CONCLUSIONS
VPA does not significantly affect PK or metabolism of MCB, whereas CBZ time‐dependently decreases MCB exposure, probably by inducing metabolism of MCB and its major plasma metabolite. The actual clinical relevance of the observed MCB–CBZ PK interaction needs to be further evaluated in a more comprehensive study.
DOI: 10.1111/j.1365-2125.2008.03326.x
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