Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study
2009
Аутори
Rakić-Ignjatović, AnitaMiljković, Branislava
Todorović, Dejan
Timotijević, Ivana
Pokrajac, Milena
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot Moclobemide (MCB) undergoes extensive both presystemic and systemic metabolism that can be affected by concomitant drugs. center dot Valproic 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-spectrum inhibitor, and CBZ as a potent inducer of a variety of drug-metabolizing enzymes. center dot There 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. WHAT THIS STUDY ADDS center dot VPA does not significantly affect PK or metabolism of MCB at steady state. center dot CBZ significantly decreases MCB exposure. This effect is time-dependent, being more pronounced after 3-5 weeks of co-administration. To assess the impact of valproic acid (VPA) and carbamazepine (CBZ) o...n moclobemide (MCB) pharmacokinetics (PK) and metabolism at steady state in depressive patients. 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. 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 C-max by 28% (from 1.911 to 1.383 mg l(-1); 95% CI -0.98197, -0.07518; P lt 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 lt 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 lt 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. 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.
Кључне речи:
carbamazepine / depression / interaction / moclobemide / pharmacokinetics / valproic acidИзвор:
British Journal of Clinical Pharmacology, 2009, 67, 2, 199-208Издавач:
- Wiley, Hoboken
Финансирање / пројекти:
- Експериментална и клиничко-фармаколошка истраживања механизма дејства и интеракција лекова у нервном и кардиоваскуларном систему (RS-MESTD-MPN2006-2010-145001)
- Institute of Mental Health in Belgrade
DOI: 10.1111/j.1365-2125.2008.03326.x
ISSN: 0306-5251
PubMed: 19076986
WoS: 000263678100007
Scopus: 2-s2.0-61349164772
Институција/група
PharmacyTY - JOUR AU - Rakić-Ignjatović, Anita AU - Miljković, Branislava AU - Todorović, Dejan AU - Timotijević, Ivana AU - Pokrajac, Milena PY - 2009 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1249 AB - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot Moclobemide (MCB) undergoes extensive both presystemic and systemic metabolism that can be affected by concomitant drugs. center dot Valproic 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-spectrum inhibitor, and CBZ as a potent inducer of a variety of drug-metabolizing enzymes. center dot There 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. WHAT THIS STUDY ADDS center dot VPA does not significantly affect PK or metabolism of MCB at steady state. center dot CBZ significantly decreases MCB exposure. This effect is time-dependent, being more pronounced after 3-5 weeks of co-administration. To assess the impact of valproic acid (VPA) and carbamazepine (CBZ) on moclobemide (MCB) pharmacokinetics (PK) and metabolism at steady state in depressive patients. 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. 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 C-max by 28% (from 1.911 to 1.383 mg l(-1); 95% CI -0.98197, -0.07518; P lt 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 lt 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 lt 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. 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. PB - Wiley, Hoboken T2 - British Journal of Clinical Pharmacology T1 - Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study VL - 67 IS - 2 SP - 199 EP - 208 DO - 10.1111/j.1365-2125.2008.03326.x ER -
@article{ author = "Rakić-Ignjatović, Anita and Miljković, Branislava and Todorović, Dejan and Timotijević, Ivana and Pokrajac, Milena", year = "2009", abstract = "WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot Moclobemide (MCB) undergoes extensive both presystemic and systemic metabolism that can be affected by concomitant drugs. center dot Valproic 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-spectrum inhibitor, and CBZ as a potent inducer of a variety of drug-metabolizing enzymes. center dot There 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. WHAT THIS STUDY ADDS center dot VPA does not significantly affect PK or metabolism of MCB at steady state. center dot CBZ significantly decreases MCB exposure. This effect is time-dependent, being more pronounced after 3-5 weeks of co-administration. To assess the impact of valproic acid (VPA) and carbamazepine (CBZ) on moclobemide (MCB) pharmacokinetics (PK) and metabolism at steady state in depressive patients. 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. 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 C-max by 28% (from 1.911 to 1.383 mg l(-1); 95% CI -0.98197, -0.07518; P lt 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 lt 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 lt 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. 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.", publisher = "Wiley, Hoboken", journal = "British Journal of Clinical Pharmacology", title = "Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study", volume = "67", number = "2", pages = "199-208", doi = "10.1111/j.1365-2125.2008.03326.x" }
Rakić-Ignjatović, A., Miljković, B., Todorović, D., Timotijević, I.,& Pokrajac, M.. (2009). Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study. in British Journal of Clinical Pharmacology Wiley, Hoboken., 67(2), 199-208. https://doi.org/10.1111/j.1365-2125.2008.03326.x
Rakić-Ignjatović A, Miljković B, Todorović D, Timotijević I, Pokrajac M. Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study. in British Journal of Clinical Pharmacology. 2009;67(2):199-208. doi:10.1111/j.1365-2125.2008.03326.x .
Rakić-Ignjatović, Anita, Miljković, Branislava, Todorović, Dejan, Timotijević, Ivana, Pokrajac, Milena, "Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study" in British Journal of Clinical Pharmacology, 67, no. 2 (2009):199-208, https://doi.org/10.1111/j.1365-2125.2008.03326.x . .