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

Overview

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.

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.