Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 53, 2023 - Issue 3
96
Views
0
CrossRef citations to date
0
Altmetric
Animal Pharmacokinetics and Metabolism

Combination of losartan and puerarin induced pharmacokinetic interaction in hypertension rats enhances the antihypertensive effect of losartan

&
Pages 201-206 | Received 14 Mar 2023, Accepted 24 Apr 2023, Published online: 02 May 2023
 

Abstract

  1. The co-administration of losartan and puerarin in hypertension rat models was investigated aiming to evaluate their interaction and potential mechanism.

  2. Hypertension rat models were established with N (omega)-nitro-L-arginine methyl ester and the pharmacokinetics and antihypertensive effect of losartan were analyzed in normal and hypertension rats. In vitro, the metabolic stability of losartan was evaluated in rat liver microsomes, and the effect of puerarin on the activity of CYP2C9 and 3A4 was assessed in human liver microsomes.

  3. Puerarin significantly changed the pharmacokinetic profiling of losartan in hypertension rats, with the behaviour of increasing AUC, AUMC, Cmax, and prolonged t1/2. The antihypertensive effect of losartan was enhanced by the co-administration of puerarin, which reduced the systolic blood pressure and diastolic blood pressure below normal levels. In vitro, puerarin significantly improved the metabolic stability of losartan with a reduced intrinsic clearance rate. Puerarin also showed significant inhibitory effects on the activity of CYP2C9 and 3A4 with the IC50 of 17.15 and 7.69 μM, respectively.

  4. Losartan co-administered with puerarin increased the system exposure and metabolic stability of losartan and enhanced its antihypertensive effect. The inhibition of CYP2C9 and 3A4 by puerarin was the potential mechanism mediating their interaction.

Disclosure statement

The authors report there are no competing interests to declare.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 65.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 897.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.