Abstract：
The current study investigated “pharmacodynamics and pharmacokinetics interactions” of losartan with Curcuma longa (CUR) and Lepidium sativum (LS) in hypertensive rats. Hypertension was induced by oral administration of L-NAME (40 mg/kg) for two weeks. Oral administration of CUR or LS shows some substantial antihypertensive activity. The systolic blood pressure (SBP) of hypertensive rats was decreased by 7.04% and 8.78% 12 h after treatment with CUR and LS, respectively, as compared to rats treated with L-NAME alone. LS and CUR display the ability to potentiate the blood pressure-lowering effects of losartan in hypertensive rats. A greater decrease in SBP, by 11.66% and 13.74%, was observed in hypertensive rats treated with CUR + losartan and LS + losartan, respectively. Further, both the investigated herbs, CUR and LS, caused an increase in plasma concentrations of losartan in hypertensive rats. The AUC0-t, AUC0-inf and AUMC0-inf of losartan were increased by 1.25-fold, 1.28-fold and 1.09-fold in hypertensive rats treated with CUR + losartan. A significant (p < 0.05) increase in AUC0-t (2.41-fold), AUC0-inf (3.86-fold) and AUMC0-inf (8.35-fold) of losartan was observed in hypertensive rats treated with LS + losartan. The present study affirms that interactions between CUR or LS with losartan alter both “pharmacokinetics and pharmacodynamics” of the drug. Concurrent administration of losartan with either CUR or LS would require dose adjustment and intermittent blood pressure monitoring for clinical use in hypertensive patients. Additional investigation is necessary to determine the importance of these interactions in humans and to elucidate the mechanisms of action behind these interactions.
摘要：
目前的研究调查了氯沙坦与姜黄（CUR）和Lepidiumsativum（LS）在高血压大鼠中的“药效学和药代动力学相互作用”。通过口服L-NAME(40mg/kg)两周诱导高血压。口服CUR或LS显示出一定的抗高血压活性。经CUR和LS治疗12h后,高血压大鼠收缩压(SBP)分别下降7.04%和8.78%,分别,与单独用L-NAME治疗的大鼠相比。LS和CUR显示出增强氯沙坦在高血压大鼠中的降血压作用的能力。SBP下降幅度更大，分别为11.66%和13.74%,在用CUR+氯沙坦和LS+氯沙坦治疗的高血压大鼠中观察到，分别。Further,两种被调查的草药，CUR和LS,引起高血压大鼠血浆氯沙坦浓度增加。AUC0-t,氯沙坦的AUC0-inf和AUMC0-inf增加了1.25倍，用CUR+氯沙坦治疗的高血压大鼠的1.28倍和1.09倍。AUC0-t显著(p<0.05)增加(2.41倍)，在用LS+氯沙坦治疗的高血压大鼠中观察到氯沙坦的AUC0-inf(3.86倍)和AUMC0-inf(8.35倍)。本研究确认CUR或LS与氯沙坦之间的相互作用会改变药物的“药代动力学和药效学”。氯沙坦与CUR或LS的同时给药需要剂量调整和间歇性血压监测，以临床用于高血压患者。需要进一步的研究来确定这些相互作用在人类中的重要性，并阐明这些相互作用背后的作用机制。
