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用于舍曲林的CYP2D6药物代谢纳米生物传感器的安培响应:一种选择性5-羟色胺再摄取抑制剂。

Amperometric responses of CYP2D6 drug metabolism nanobiosensor for sertraline: a selective serotonin reuptake inhibitor.

作者信息

Iwuoha E, Ngece R, Klink M, Baker P

机构信息

University of the Western Cape, Sensor Research Laboratory, Department of Chemistry, Cape Town, South Africa.

出版信息

IET Nanobiotechnol. 2007 Aug;1(4):62-7. doi: 10.1049/iet-nbt:20070005.

DOI:10.1049/iet-nbt:20070005
PMID:17672807
Abstract

Sertraline is selective serotonin reuptake inhibitor drug marketed as Zoloft by Pfizer and used mainly for the treatment of depression, anxiety and obsession. A number of side effects are associated with the use of the drug including gastrointestinal complaints, nervousness and sexual dysfunction. This means that a reliable fast method (such as biosensing) for determining sertraline metabolic profile of patients is essential for adequate dosing. Nanobiosensor for the determination of sertraline biotransformation was prepared with cytochrome P450-2D6 (CYP2D6) and poly(8-anilino-1-napthalene sulphonic acid) nanotubes (90 nm in diameter and 600-800 nm in length) potentiodynamically deposited on gold. The biosensor gave a linear response over the concentration range of 0.2 and 1.4 microM with a sensitivity value of 0.301 microA/microM and a detection limit of 0.13 microM. The nanobiosensor exhibited substrate inhibition response profile for sertraline biotransformation at high concentrations. Analysis of the Michaelis-Menten region of the nanosensor response curve for sertraline gave an apparent Michaelis-Menten constant (K(m)) value of 0.75 microM, which is higher than the peak plasma concentration (C(max)) value of 0.55 microM, thereby making the sensor suitable for sertraline determination in serum.

摘要

舍曲林是一种选择性5-羟色胺再摄取抑制剂药物,由辉瑞公司以左洛复的名称上市销售,主要用于治疗抑郁症、焦虑症和强迫症。使用该药物会产生一些副作用,包括胃肠道不适、紧张和性功能障碍。这意味着,一种可靠的快速方法(如生物传感)对于确定患者的舍曲林代谢情况以实现适当给药至关重要。用于测定舍曲林生物转化的纳米生物传感器是通过将细胞色素P450-2D6(CYP2D6)和聚(8-苯胺基-1-萘磺酸)纳米管(直径90纳米,长度600-800纳米)恒电位沉积在金上制备而成的。该生物传感器在0.2至1.4微摩尔的浓度范围内呈现线性响应,灵敏度值为0.301微安/微摩尔,检测限为0.13微摩尔。该纳米生物传感器在高浓度下对舍曲林生物转化表现出底物抑制响应曲线。对舍曲林纳米传感器响应曲线的米氏区域分析得出表观米氏常数(K(m))值为0.75微摩尔,高于0.55微摩尔的血浆峰值浓度(C(max))值,因此该传感器适用于血清中舍曲林的测定。

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