Ahad Abdul, Raish Mohammad, Bin Jardan Yousef A, Alam Mohd Aftab, Al-Mohizea Abdullah M, Al-Jenoobi Fahad I
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Xenobiotica. 2020 Jul;50(7):847-857. doi: 10.1080/00498254.2020.1729446. Epub 2020 Mar 5.
The present study aimed to determine the effect of and on antihypertensive activity and pharmacokinetic of losartan in hypertensive rats.Hypertension was induced in rats by oral administration of L-NAME (40 mg/kg per day). Pharmacodynamics and pharmacokinetics of losartan were evaluated without and with herbal treatment in hypertensive rats.Treatment of hypertensive rats with investigated herbs substantially reduced systolic blood pressure (SBP), and diastolic blood pressure (DBP) of rats. Treatment of rats ( = 5) with L-NAME plus H. plus losartan and L-NAME plus Z. plus losartan reduced SBP by 16.20% and 14.88% and DBP by 14.82% and 17.52% respectively after 12 h, as compared to L-NAME alone treated rats. In a pharmacokinetic study, the C and AUC of losartan in L-NAME plus H. plus losartan and L-NAME plus Z. plus losartan treated rats was increased by 0.7, 1.99 and 1.51, 3.00 fold respectively in comparison to the C and AUC obtained for L-NAME plus losartan treated group. In conclusion, both the investigated herbs significantly increased the antihypertensive effect and plasma concentration of losartan in L-NAME induced hypertensive rats. The current study predicted that the herb-drug interaction between H. -losartan and Z. -losartan could occur; hence these results in rats may warrant further studies in humans, either in humans or in human liver microsomes.
本研究旨在确定[两种草药名称未给出]对洛沙坦在高血压大鼠中的降压活性和药代动力学的影响。通过口服L-NAME(每天40毫克/千克)诱导大鼠高血压。在高血压大鼠中,评估了洛沙坦在有无草药治疗情况下的药效学和药代动力学。用所研究的草药治疗高血压大鼠可显著降低大鼠的收缩压(SBP)和舒张压(DBP)。与仅用L-NAME治疗的大鼠相比,用L-NAME加[第一种草药名称未给出]加洛沙坦和L-NAME加[第二种草药名称未给出]加洛沙坦治疗大鼠(n = 5)12小时后,SBP分别降低了16.20%和14.88%,DBP分别降低了14.82%和17.52%。在药代动力学研究中,与L-NAME加洛沙坦治疗组相比,L-NAME加[第一种草药名称未给出]加洛沙坦和L-NAME加[第二种草药名称未给出]加洛沙坦治疗的大鼠中洛沙坦的Cmax和AUC分别增加了0.7、1.99倍和1.51、3.00倍。总之,两种所研究的草药均显著增强了洛沙坦在L-NAME诱导的高血压大鼠中的降压作用和血浆浓度。本研究预测H.[第一种草药名称未给出]-洛沙坦和Z.[第二种草药名称未给出]-洛沙坦之间可能发生草药-药物相互作用;因此,大鼠中的这些结果可能需要在人体或人肝微粒体中进行进一步的人体研究。