Ravindra R P, Arunkumar S, Puniyani R R, Padgaonkar K, Vadivelu Ramalingam, Sharma Rajeev, Panicker Gopi, Lokhandwala Yash
School of Biosciences and Bioengineering, Indian Institute of Technology, Bombay, Powai, Mumbai 400076, India.
From Drug Monitoring Research Institute, 125-A, Sion, Mumbai 400022, India.
Indian Heart J. 2019 Jan-Feb;71(1):32-38. doi: 10.1016/j.ihj.2018.10.417. Epub 2018 Dec 4.
Despite several decades of use of calcium channel blockers, the side effect of edema persists as a class effect, and its mechanism is unresolved. Amlodipine has effects on hemorheology (HR), and its hemodilutory property may partly contribute to its antihypertensive action. This aspect is not well studied, and the literature is sparse in this regard.
This experiment was planned to determine effect of a single-dose administration of amlodipine on HR parameters in normal human volunteers.
Amlodipine (5 mg) or S (-) amlodipine (2.5 mg) was administered to 27 normal human volunteers. Whole-blood viscosity (WBV) at different shear rates, plasma viscosity (PV), red cell rigidity (RCR), red cell aggregation (RCA), hematocrit (Hct), plasma hemoglobin, along with plasma drug concentration were determined at time intervals, t = 0, 4, 8, 12, and 24 h. Statistically significant reductions were observed at t = 4 h in WBV at shear rates of 0.512 s (p < 0.005), WBV at shear rates of 5.26 s (p < 0.01), PV (p < 0.05), and Hct (p < 0.01). At t = 8 h, as drug concentration reduced, some of the changes persisted and later slowly decreased with the decreasing drug concentration till t = 24 h. Red blood cell-related parameters such as RCA and RCR remained unaltered. WBV values at all shear rates, when corrected for Hct = 0.45, did not show deviation from their original values at any time.
Amlodipine causes a reduction in Hct and blood viscosity, along with hemodilution. These effects persist as long as the drug remains in plasma. Edema resulting from chronic dosing may be explained by the aforementioned effects. It is possible that antihypertensive action of the drug may be due to a combination of vasodilatation and an improvement in the HR properties.
尽管钙通道阻滞剂已使用数十年，但水肿这一副作用作为该类药物的共性问题依然存在，其机制尚未明确。氨氯地平对血液流变学（HR）有影响，其血液稀释特性可能部分有助于其降压作用。这方面的研究尚不充分，相关文献也较为匮乏。
本实验旨在确定单剂量氨氯地平对正常人类志愿者血液流变学参数的影响。
对27名正常人类志愿者给予氨氯地平（5毫克）或S（-）氨氯地平（2.5毫克）。在时间点t = 0、4、8、12和24小时测定不同剪切速率下的全血粘度（WBV）、血浆粘度（PV）、红细胞刚性（RCR）、红细胞聚集（RCA）、血细胞比容（Hct）、血浆血红蛋白以及血浆药物浓度。在t = 4小时时，观察到剪切速率为0.512秒时的WBV（p < 0.005）、剪切速率为5.26秒时的WBV（p < 0.01）、PV（p < 0.05）和Hct（p < 0.01）有统计学意义的降低。在t = 8小时时，随着药物浓度降低，一些变化持续存在，随后随着药物浓度降低而缓慢下降直至t = 24小时。红细胞相关参数如RCA和RCR保持不变。当血细胞比容校正为0.45时，所有剪切速率下的WBV值在任何时候均未显示偏离其原始值。
氨氯地平可导致Hct和血液粘度降低以及血液稀释。只要药物存在于血浆中，这些作用就会持续。长期给药引起的水肿可能可以用上述作用来解释。该药物的降压作用可能是血管舒张和血液流变学特性改善共同作用的结果。
