The impact of CYP2C19 genotypes on steady-state plasma concentration of escitalopram in South Indian population with Major Depressive Disorder

B. Jeevan Kumar, Vijayakumar Thangavel Mahalingam, Ganesh Kumar M
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Abstract

Background: Among depressed patients, escitalopram plasma levels differed between those who were considered as extensive metabolizers and poor metabolizers of CYP2C19. However, the majority of research utilized the dose-response relationship. Consequently, we investigated the effect of variations in the CYP2C19 gene on the levels of drug in the bloodstream of individuals suffering from Major Depressive Disorder (MDD) in south India. Methods: A total of 109 individuals with MDD who were prescribed escitalopram at doses of 5, 10, 15, or 20 mg daily participated in this research. We used HPLC with SPD-10AVP UV-Visible detector to measure the escitalopram concentrations in the blood. The polymorphisms of the CYP2C19 were determined by employing the PCR techniques. Results: Our study found that 55% of the subjects were intermediate metabolizers, followed by extensive (19.3%), poor (17.4%), and ultra-rapid (8.3%). The significant correlation is identified between the steady state plasma concentration and Sex with (P - Value < 0.05), insignificant correlation was seen in Age and BMI with (P - Value > 0.05). The majority of gene variants seen in the study population were CYP2C19*1/*2, accounting for 49 individuals (44.9%). Conclusion: These findings showed that sex had a substantial impact on the CYP2C19 genetic variation. Medication administration to individuals with CYP2C19PM requires special caution.
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南印度重度抑郁症患者 CYP2C19 基因型对艾司西酞普兰稳态血浆浓度的影响
研究背景在抑郁症患者中,CYP2C19广泛代谢者和不良代谢者的艾司西酞普兰血浆水平存在差异。然而,大多数研究利用的是剂量-反应关系。因此,我们在印度南部调查了 CYP2C19 基因变异对重度抑郁症(MDD)患者血液中药物水平的影响。研究方法共有 109 名重度抑郁症患者参与了这项研究,他们每天服用 5、10、15 或 20 毫克剂量的艾司西酞普兰。我们使用 HPLC 和 SPD-10AVP 紫外可见检测器来测量血液中的艾司西酞普兰浓度。采用 PCR 技术测定了 CYP2C19 的多态性。研究结果我们的研究发现,55% 的受试者为中度代谢者,其次是广泛代谢者(19.3%)、低代谢者(17.4%)和超快速代谢者(8.3%)。稳态血浆浓度与性别之间存在明显的相关性(P 值小于 0.05),年龄与体重指数之间的相关性不明显(P 值大于 0.05)。研究人群中出现的大多数基因变异为 CYP2C19*1/*2,占 49 人(44.9%)。结论这些研究结果表明,性别对 CYP2C19 基因变异有很大影响。对 CYP2C19PM 患者用药需要特别谨慎。
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