<abstract xmlns="http://www.w3.org/1999/xhtml">Depression is a common mental disorder affecting more than 264 million people in the world and 5.1% of the Slovak population. Although various antidepressant approaches have been used; still, about 40% of patients do not respond to a first-choice drug administration and one third of patients do not achieve total remission. Therapeutic drug monitoring (TDM) is a method used for quantification and interpreting the drug concentrations in plasma in order to optimize the pharmacotherapy. The aim of this study was to measure the plasma concentrations of venlafaxine, the fourth most prescribed antidepressant in Slovakia, as well as its active metabolite and interpret them with the relevant patients’ characteristics.The study was of retrospective nature and 28 adult patients in total were included. The concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) in plasma were quantified using the validated UHPLC-MS/MS method. The effects of potential influencing factors were evaluated by a multivariate linear regression model.Only 39% of patients reached the venlafaxine active moiety concentrations within the recommended therapeutic range. Plasma concentrations were dependent on age, gender, and duration of the therapy. Venlafaxine metabolism expressed as a metaboliteto-parent concentrations ratio was influenced by a combination of age, gender, and body mass index (BMI). We did not observe any significant difference in plasma concentrations between the patients with a single and recurrent diagnosis of depression. Combining variables made an additive effect on plasma concentrations, for example, active moiety plasma concentrations were higher in older women. In contrast, drug metabolism was higher in older men and men with lower BMI. TDM of venlafaxine is recommended in clinical practice, especially in the elderly when beginning the pharmacotherapy.</abstract>

Depression is a common mental disorder affecting more than 264 million people in the world and 5.1% of the Slovak population. Although various antidepressant approaches have been used; still, about 40% of patients do not respond to a first-choice drug administration and one third of patients do not achieve total remission. Therapeutic drug monitoring (TDM) is a method used for quantification and interpreting the drug concentrations in plasma in order to optimize the pharmacotherapy. The aim of this study was to measure the plasma concentrations of venlafaxine, the fourth most prescribed antidepressant in Slovakia, as well as its active metabolite and interpret them with the relevant patients’ characteristics.The study was of retrospective nature and 28 adult patients in total were included. The concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) in plasma were quantified using the validated UHPLC-MS/MS method. The effects of potential influencing factors were evaluated by a multivariate linear regression model.Only 39% of patients reached the venlafaxine active moiety concentrations within the recommended therapeutic range. Plasma concentrations were dependent on age, gender, and duration of the therapy. Venlafaxine metabolism expressed as a metaboliteto-parent concentrations ratio was influenced by a combination of age, gender, and body mass index (BMI). We did not observe any significant difference in plasma concentrations between the patients with a single and recurrent diagnosis of depression. Combining variables made an additive effect on plasma concentrations, for example, active moiety plasma concentrations were higher in older women. In contrast, drug metabolism was higher in older men and men with lower BMI. TDM of venlafaxine is recommended in clinical practice, especially in the elderly when beginning the pharmacotherapy.

Therapeutic Drug Monitoring of Venlafaxine and Impact of Age, Gender, BMI, and Diagnosis

Department of Pharmacology, Jessenius Faculty of Medicine

Comenius University in Martin and University Hospital Martin

Department of Physiology, Jessenius Faculty of Medicine

European Pharmaceutical Journal

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Depression is a common mental disorder affecting more than 264 million people in the world and 5.1% of the Slovak population. Although various antidepressant...

	Patients	VEN [ng/mL]	ODV [ng/mL]	ODV/VEN	ODV+VEN [ng/mL]
All	25	182	345	1.85	452
Females	15	255	370	1.85	693
Males	10	148	261	1.75	389
Age < 65	21	132	304	1.92	417
Age ≥ 65	4	345	511	1.55	859
F32	7	128	280	2.00	435
F33	18	198	356	1.74	553

	Patients	DCC [ng/mL/mg]
All	28	1.46
Females	16	2.07
Males	12	1.30
Age < 65	24	1.39
Age ≥ 65	4	2.86
F32	8	1.46
F33	20	1.61

Therapeutic Drug Monitoring of Venlafaxine and Impact of Age, Gender, BMI, and Diagnosis

Article Category: Original Paper

Published Online: Nov 18, 2020

Page range: 33 - 37

Received: Feb 28, 2020

Accepted: Jun 24, 2020

DOI: https://doi.org/10.2478/afpuc-2020-0005

Keywords
Venlafaxine, major depressive disorder, therapeutic drug monitoring

© 2019 Krivosova M. et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Medians of plasma concentrations (VEN and ODV; ODV+VEN) and metabolite to parent drug ratios (ODV/VEN) in patients treated with venlafaxine at the single daily dose of 300 mg (F32 – single episode of MDD; F33 – recurrent episode of MDD)

Medians of dose-corrected plasma concentrations (DCC) of venlafaxine active moiety (F32 – single episode of MDD; F33 – recurrent episode of MDD)

Therapeutic Drug Monitoring of Venlafaxine and Impact of Age, Gender, BMI, and Diagnosis

Article Category: Original Paper

Published Online: Nov 18, 2020

Page range: 33 - 37

Received: Feb 28, 2020

Accepted: Jun 24, 2020

DOI: https://doi.org/10.2478/afpuc-2020-0005

KeywordsVenlafaxine, major depressive disorder, therapeutic drug monitoring

© 2019 Krivosova M. et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Medians of plasma concentrations (VEN and ODV; ODV+VEN) and metabolite to parent drug ratios (ODV/VEN) in patients treated with venlafaxine at the single daily dose of 300 mg (F32 – single episode of MDD; F33 – recurrent episode of MDD)

Medians of dose-corrected plasma concentrations (DCC) of venlafaxine active moiety (F32 – single episode of MDD; F33 – recurrent episode of MDD)

Keywords
Venlafaxine, major depressive disorder, therapeutic drug monitoring