Assessment of the relationship between drug level and cytochrome p450 enzyme activities in patients demanding genetic polymorphism and escitalopram monitorization

Therapeutic Drug Monitorization (TDM) is used to determine the concentration of drug in plasma to adjust the dose of therapeutic drug. Selective and sensitive analytical methods are used to determine drug and metabolite levels for the successful application of TDM. The aim of the study was to develop and validate a new method using liquid chromatography mass spectrometry (LC-MS / MS) to analyze quantitative assay of escitalopram ( S-CT) and its metabolites in human plasma and urine samples. Also, association between metabolic ratio (MR) of S-CT and its metabolites and cytochrome P450 enzyme activities (CYP2C19 and CYP2D6) of patients were assessed using this validated method in order to determine individual pharmacokinetic characteristics. It is thought that besides knowing the pharmacokinetic characteristics of patients, pharmacodynamics characteristics of individuals have an essential role in increasing the success of the treatment. Therefore, serotonin transporter protein (5-HTT) polymorphism distribution of the same patients was examined as well. With the study, it is aimed that it could help the physician provide a convenient and safe treatment dose for the patients. In this study, plasma and urine samples collected from patients using escitalopram as part of their treatment in NPİstanbul Brain Hospital were analyzed by LC-MS / MS at Üsküdar University Clinical Pharmacogenetic Laboratory and the concentration of S-CT, dimethyl escitalopram (S-DCT) and didemethyl escitalopram (S-DDCT) were measured. In addition, a genotyping study was performed from whole blood samples taken to identify CYP2C19, CYP2D6 and pharmacodynamic (5-HTT) polymorphisms of the same patients and statistical evaluation was performed by looking at the relationship between blood level results and MR of patients with their genotyping results. The mean S-DCT and S-DDCT concentrations of the 30 patients with mean plasma escitalopram concentration of 27.59 ng/mL were 85.52 ng/mL and 44.30 ng/mL, respectively. The mean S-CT / S-DCT value of the S-CT, metabolized to the S-DCT by the CYP2C19 enzyme as the major pathway, was calculated to be 0.40. In this study, it is found that the mean MR of patients in the CYP2C19 EM and IM groups is different compared to the UM group. Therefore, it is thought that by considering the S-CT / S-DCT value for many patients without genotyping analysis, a pre-assessment can be made regarding the CYP2C19 enzyme activity. Also, it is found that the mean MR of patients in the CYP2D6 EM and CYP2D6 Het. EM group is different compared to the CYP2D6 IM group. When the response of 30 patients to drug treatment with 5-HTT polymorphism distribution of patients was examined, it was observed that the difference between the groups was statistically significant (p <0.05). While a statistical significance ( p < 0.05) was detected between LL (long:long) and SS (short:short) groups in reponse to treatment, no statistical significance in the response to treatment was found between the LS (long:short) group and the other groups (p> 0.05). Evaluation of the data obtained from our study by physicians is thought to be able to contribute treatment of patients in the application of individual drug treatment.