CYP1A2, ABCB1, CYP2C9 and Plasma Concentration of Agomelatine in Adult Patients With Depression

Depression Clinical Trial

Official title:

Correlation Between CYP1A2, ABCB1, CYP2C9 Gene Polymorphisms and Plasma Concentration of Agomelatine and Its Metabolites in Adult Patients With Depression

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06120543
• Other study ID #: wangqin01
• Status: Not yet recruiting
• Start date: October 31, 2023
• Est. completion date: March 31, 2025

Study information

• Verified date: August 2023
• Source: Affiliated Hospital of Nantong University
• Contact: Qin Wang
• Phone: +8618921600968
• Email: wangqin[@]ntu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

1. The plasma concentrations of agomelatine and its two metabolites are simultaneously determined by High performance liquid chromatography-tandem mass spectrometry;

2. The gene polymorphisms of CYP1A2, ABCB1 and CYP2C9 are detected by fluorescence in situ hybridization or fluorescence polymerase chain reaction;

3. The correlation of CYP1A2, ABCB1, CYP2C9 gene polymorphisms with the blood concentration of agomelatine and its two metabolites is investigated by pharmacokinetic study;

4. According to the correlation between the above genotypes and blood drug concentration, a lean medication guidance scheme for agomelatine will be formed.

Description:

1. research purpose and significance Through blood concentration monitoring, pharmacokinetics and gene detection technology, combined with clinical prospective research, the lean medication of agomelatine will be achieved. Objective to establish a method for analyzing the blood concentration of agomelatine and its two metabolites, which can be applied to routine detection in hospital. Objective to search for the genes related to the metabolism of agomelatine in vivo, and to detect the polymorphisms of related genes quickly and easily by fluorescence in situ hybridization or micro sequencing technology. Objective to explore the correlation between gene polymorphism and blood concentration of agomelatine and its two metabolites, and to make reasonable pharmaceutical recommendations for clinical lean drug use.

2. research content and design The plasma concentrations of agomelatine and its two metabolites are simultaneously detected by High performance liquid chromatography-tandem mass spectrometry; The gene polymorphisms of CYP1A2, ABCB1 and CYP2C9 are detected by fluorescence in situ hybridization or microsequencing; Objective to explore the correlation between CYP1A2, ABCB1, CYP2C9 gene polymorphisms and the blood concentration of agomelatine and its two metabolites by pharmacokinetic study.

3. research object

50 adult depression patients taking agomelatine

4 research steps

1. The plasma concentrations of agomelatine and its two metabolites are simultaneously detected by High performance liquid chromatography-tandem mass spectrometry;

2. The gene polymorphisms of CYP1A2, ABCB1 and CYP2C9 are detected by fluorescence in situ hybridization or fluorescence polymerase chain reaction;

3. The correlation of CYP1A2, ABCB1, CYP2C9 gene polymorphisms with the blood concentration of agomelatine and its two metabolites is investigated by pharmacokinetic study;

4. According to the correlation between the above genotypes and blood drug concentration, a lean medication guidance scheme for agomelatine will be formed.

5 evaluation index

1. The blood drug concentration monitoring method should have a certain degree of precision and accuracy, and meet the relevant requirements of the Chinese Pharmacopoeia; The gene detection method is required to be fast and simple, and the internal and external quality control should be carried out;

2. The medical record data should be collected completely, the privacy of patients should be respected, and the blood sample storage should meet the relevant conditions through the review of the hospital ethics committee;

3. The refined medication guidance scheme of agomelatine can be formed based on the data of therapeutic drug monitoring, gene detection and clinical research.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: March 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

Inclusion Criteria:

Clinical diagnosis of depression; Sleep disorder.

Exclusion Criteria:

Mental disorder; Intelligence disorder; Dementia; Aphasia; Dysarthria; Consciousness disorder; Severe heart, kidney or liver dysfunction; Pregnant and lactating women; Malignant tumor.

Related Conditions & MeSH terms

• CYP1A2 Polymorphism
• Depression
• Depressive Disorder
• Plasma Concentration
• Polymerase Chain Reaction
• Polymorphism, Genetic

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Affiliated Hospital of Nantong University

References & Publications (10)

Arango C, Buitelaar JK, Fegert JM, Olivier V, Penelaud PF, Marx U, Chimits D, Falissard B; study investigators. Safety and efficacy of agomelatine in children and adolescents with major depressive disorder receiving psychosocial counselling: a double-blind, randomised, controlled, phase 3 trial in nine countries. Lancet Psychiatry. 2022 Feb;9(2):113-124. doi: 10.1016/S2215-0366(21)00390-4. Epub 2021 Dec 14. Erratum In: Lancet Psychiatry. 2022 Mar;9(3):e10. — View Citation

El-Deen AK, Magdy G, Shimizu K. A reverse micelle-mediated dispersive liquid-liquid microextraction coupled to high-performance liquid chromatography for the simultaneous determination of agomelatine and venlafaxine in pharmaceuticals and human plasma. J — View Citation

Guardiola-Lemaitre B, De Bodinat C, Delagrange P, Millan MJ, Munoz C, Mocaer E. Agomelatine: mechanism of action and pharmacological profile in relation to antidepressant properties. Br J Pharmacol. 2014 Aug;171(15):3604-19. doi: 10.1111/bph.12720. — View Citation

Konstantakopoulos G, Dimitrakopoulos S, Michalopoulou PG. The preclinical discovery and development of agomelatine for the treatment of depression. Expert Opin Drug Discov. 2020 Oct;15(10):1121-1132. doi: 10.1080/17460441.2020.1781087. Epub 2020 Jun 22. — View Citation

Li M, Tang F, Xie F, Lv Y, Yu P, Liu Z, Cheng Z. Development and validation a LC-MS/MS method for the simultaneous determination of agomelatine and its metabolites, 7-desmethyl-agomelatine and 3-hydroxy-agomelatine in human plasma: Application to a bioequ — View Citation

Maddukuri RK, Hema C, Sri Tejaswi K, Venkata Mounika M, Vegesana BP. Antidepressant efficacy of Agomelatine: Meta-analysis of placebo controlled and active comparator studies. Asian J Psychiatr. 2021 Nov;65:102866. doi: 10.1016/j.ajp.2021.102866. Epub 2021 Sep 20. — View Citation

Saiz-Rodriguez M, Ochoa D, Belmonte C, Roman M, Vieira de Lara D, Zubiaur P, Koller D, Mejia G, Abad-Santos F. Polymorphisms in CYP1A2, CYP2C9 and ABCB1 affect agomelatine pharmacokinetics. J Psychopharmacol. 2019 Apr;33(4):522-531. doi: 10.1177/026988111 — View Citation

San L, Arranz B. Agomelatine: a novel mechanism of antidepressant action involving the melatonergic and the serotonergic system. Eur Psychiatry. 2008 Sep;23(6):396-402. doi: 10.1016/j.eurpsy.2008.04.002. Epub 2008 Jun 25. — View Citation

Xie F, Vermeulen A, Colin P, Cheng Z. A semiphysiological population pharmacokinetic model of agomelatine and its metabolites in Chinese healthy volunteers. Br J Clin Pharmacol. 2019 May;85(5):1003-1014. doi: 10.1111/bcp.13902. Epub 2019 Mar 21. — View Citation

Zhang H, Pu C, Wang Q, Tan X, Gou J, He H, Zhang Y, Yin T, Wang Y, Tang X. Physicochemical Characterization and Pharmacokinetics of Agomelatine-Loaded PLGA Microspheres for Intramuscular Injection. Pharm Res. 2018 Nov 8;36(1):9. doi: 10.1007/s11095-018-25 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentration of Agomelatine	Plasma concentration of Agomelatine	3 hours after the patients take agomelatine
Primary	CYP1A2, ABCB1, and CYP2C9 genotypes	CYP1A2, ABCB1, and CYP2C9 gene polymorphism	3 hours after the patients take agomelatine
Primary	Plasma concentration of Agomelatine metabolites	Plasma concentration of Agomelatine metabolites	3 hours after the patients take agomelatine