The effect of gender and body mass index (BMI) on the pharmacokinetics of rivastigmine was studied in Egyptian human subjects using new bio-analytical validated LC/MS/MS method. In this study, Rivastigmine was estimated in human plasma using Escitalopram as an internal standard (IS). Rivastigmine and Escitalopram were extracted from human plasma samples by liquid–liquid extraction using diethyl ether (DEE)–dichloromethane (DCM) (70:30, v/v). Chromatographic separation was performed on a reversed phase C18 INERTSIL ODS column using 0.05% aqueous formic acid, acetonitrile in the ratio (50:50, v/v) as a mobile phase. Multiple reaction monitoring (MRM) was applied and operated by positive mode electrospray ionization. A significant difference between male and female Cmax (maximum plasma concentration) (P = 0.0205; CL = 95.4) was found using Mann–Whitney U test. Also, a moderate negative correlation was found between BMI and Tmax (time to peak plasma concentration) using spearman rho test. The calculated results confirm the difference of Rivastigmine pharmacokinetics between male and female subjects. Furthermore, it indicates that Rivastigmine dose adjustment may be necessary. The method was applied for the estimation of pharmacokinetic parameters in volunteers (n = 26, 17 male and 9 female) and the effects of gender and BMI were investigated.

中文翻译：

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经验证的 LC/MS/MS 方法用于测定人血浆中的卡巴拉汀：应用于埃及志愿者的药代动力学研究以确定性别和体重指数的影响

使用经过生物分析验证的新 LC/MS/MS 方法在埃及人类受试者中研究了性别和体重指数 (BMI) 对卡巴拉汀药代动力学的影响。在这项研究中，使用艾司西酞普兰作为内标 (IS)，估计了人血浆中卡巴拉汀的含量。使用二乙醚 (DEE)-二氯甲烷 (DCM)（70:30，v/v）通过液-液萃取从人血浆样品中提取卡巴拉汀和艾司西酞普兰。色谱分离在反相 C18 INERTSIL ODS 柱上进行，使用 0.05% 甲酸水溶液、乙腈（50:50，v/v）作为流动相。应用多反应监测 (MRM) 并通过正模式电喷雾电离进行操作。男性和女性 Cmax（最大血浆浓度）之间存在显着差异（P = 0.0205；CL = 95。4) 是使用 Mann–Whitney U 检验发现的。此外，使用 spearman rho 检验发现 BMI 和 Tmax（达到血浆浓度峰值的时间）之间呈中度负相关。计算结果证实了卡巴拉汀药代动力学在男性和女性受试者之间的差异。此外，它表明卡巴拉汀的剂量调整可能是必要的。该方法用于估计志愿者（n = 26、17 名男性和 9 名女性）的药代动力学参数，并研究了性别和 BMI 的影响。