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