Pencil Graphite Electrode Decorated with Xylenol Orange Flakes for Studying Possible Pharmacokinetic Interaction Between Vardenafil and Daclatasvir,Electroanalysis

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Pencil Graphite Electrode Decorated with Xylenol Orange Flakes for Studying Possible Pharmacokinetic Interaction Between Vardenafil and Daclatasvir
Electroanalysis ( IF 2.7 ) Pub Date : 2019-12-10 , DOI: 10.1002/elan.201900272
Abdel‐Maaboud I. Mohamed ₁ , Azza H. Rageh ₁ , Fatma A. M. Abdel‐aal ₁ , Al‐Montaser Bellah H. Ali ₁

Affiliation

The main aim of the current work is to investigate possible pharmacokinetic interactions between vardenafil hydrochloride (VAR), which is used for the treatment of erectile dysfunction and daclatasvir dihydrochloride (DAC), which is used for the treatment of chronic hepatitis C viral infection when they are concomitantly administered. Therefore, a sensitive and selective square‐wave voltammetric method was developed and validated for simultaneous determination of VAR and DAC using disposable pencil graphite electrode (PGE) modified with xylenol orange (X.O.) flakes as an electrochemical sensor. A full investigation of the experimental parameters for obtaining the highest electroanalytical signal with sufficient resolution between the oxidation peaks of two compounds was performed. It was found that VAR and DAC were resolved on X.O./PGE with different potentials at 1.4 V and 0.9 V, respectively using Britton‐Robinson buffer (pH 2.2) and 0.1 mol L⁻¹ KCl as a supporting electrolyte. In addition, with the aid of cyclic voltammetry, a mechanistic scheme for the oxidation behaviour of both VAR and DAC was suggested. The proposed square wave voltammetric method was successfully applied for trace quantification of VAR and DAC in male rabbits. The suggested approach shows detection and quantification limits in rabbit plasma samples of 0.06 and 0.17 μmol L⁻¹, respectively for VAR and 0.13 and 0.39 μmol L⁻¹, respectively for DAC. The pharmacokinetic parameters of VAR alone and in combination with DAC after oral administration to rabbits were successfully estimated. The obtained results confirm that when DAC is co‐administered with VAR, plasma concentration of VAR increases, which necessitates dose adjustment for VAR to prevent toxicological consequences in patients.

中文翻译：

用二甲酚橙片装饰的铅笔状石墨电极，用于研究伐地那非与达克他韦之间可能的药代动力学相互作用

当前工作的主要目的是研究用于治疗勃起功能障碍的盐酸伐地那非（VAR）与用于治疗慢性丙型肝炎病毒感染的盐酸达卡他韦（DAC）之间可能存在的药代动力学相互作用。同时服用。因此，开发了一种灵敏且选择性的方波伏安法，并通过使用用二甲苯酚橙（XO）薄片修饰的一次性笔形石墨电极（PGE）作为电化学传感器，对同时测定VAR和DAC进行了验证。对实验参数进行了全面研究，以获取具有最高分辨力的两种化合物的氧化峰之间的最高电分析信号。发现在XO上解决了VAR和DAC^-1 KCl作为支持电解质。此外，借助循环伏安法，提出了一种针对VAR和DAC氧化行为的机理方案。所提出的方波伏安法已成功地用于雄性兔中VAR和DAC的痕量定量。该建议的方法示出了检测和定量限为0.06和0.17微摩尔大号兔血浆样品中的^-1，分别为VAR和0.13和0.39微摩尔大号^-1，分别用于DAC。成功评估了单独的VAR以及与DAC口服后与DAC联合使用的VAR的药代动力学参数。获得的结果证实，当DAC与VAR并用时，VAR的血浆浓度会增加，这需要调整VAR的剂量以防止对患者的毒理学后果。

更新日期：2019-12-11

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