Dadashzadeh S, Javadian B, Sadeghian S
Department of Pharmaceutics, Faculty of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
Biopharm Drug Dispos. 2006 Oct;27(7):329-34. doi: 10.1002/bdd.512.
The effects of gender on the pharmacokinetics of verapamil and its active metabolite, norverapamil, following single oral dose (80 mg, Isoptin) to 12 healthy male (mean age: 25.75+/-2.42 years, mean body weight: 70.59+/-9.94 kg) and 12 healthy female subjects (mean age: 24.08+/-2.84 years, mean body weight: 56.67+/-5.23 kg) were investigated in the present study. Plasma concentrations of verapamil and norverapamil were analysed using a modified high-pressure liquid chromatography method. Pharmacokinetic parameters were calculated by non-compartmental analysis for each subject. For verapamil the half-life (t1/2) and mean residence time (MRT) were significantly shorter in women than men (p<0.01 and p<0.05, respectively). For other pharmacokinetic parameters of verapamil there were no significant differences between males and females. For norverapamil, t1/2, MRT and time to reach to the maximum plasma concentration (Tmax) showed statistically significant differences between the two genders. The AUC(0-24) and AUC(0-infinity) ratios of norverapamil to verapamil were also calculated. The ratios were significantly higher in women compared with men. These observations indicate that the elimination rate of verapamil is faster in women than men which may be attributed to the higher activity of CYP3A4 or lower activity of P-glycoprotein in women compared with men. A contribution of both factors in the appearance of gender differences in verapamil pharmacokinetics is also possible.
本研究调查了性别对维拉帕米及其活性代谢产物去甲维拉帕米药代动力学的影响，研究对象为12名健康男性（平均年龄：25.75±2.42岁，平均体重：70.59±9.94kg）和12名健康女性（平均年龄：24.08±2.84岁，平均体重：56.67±5.23kg），他们单次口服剂量为80mg的维拉帕米（异搏定）。采用改良的高压液相色谱法分析血浆中维拉帕米和去甲维拉帕米的浓度。通过非房室分析计算每个受试者的药代动力学参数。对于维拉帕米，女性的半衰期（t1/2）和平均驻留时间（MRT）显著短于男性（分别为p<0.01和p<0.05）。对于维拉帕米的其他药代动力学参数，男性和女性之间没有显著差异。对于去甲维拉帕米，t1/2、MRT和达到最大血浆浓度的时间（Tmax）在两种性别之间显示出统计学上的显著差异。还计算了去甲维拉帕米与维拉帕米的AUC(0-24)和AUC(0-∞)比值。女性的比值显著高于男性。这些观察结果表明，女性体内维拉帕米的消除率比男性更快，这可能归因于女性体内CYP3A4活性较高或P-糖蛋白活性较低。这两个因素也可能共同导致维拉帕米药代动力学出现性别差异。
