Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism

Abstract

Context: Ligustrazine and valsartan are commonly used drugs in the treatment of cardiac and cardiovascular disease. Objective: The interaction between ligustrazine and valsartan was studied to investigate the effect of ligustrazine on the pharmacokinetics of valsartan. Materials and methods: The pharmacokinetics of valsartan (10 mg/kg) was investigated in Sprague-Dawley rats divided into three groups (with the pretreatment of 4 or 10 mg/kg/day ligustrazine for 10 days and without the pretreatment of ligustrazine as control) of six rats each. The in vitro experiments in rat liver microsomes were performed to explore the effect of ligustrazine on the metabolic stability of valsartan. Results: Ligustrazine changed the pharmacokinetic profile of valsartan. In the presence of 4 mg/kg ligustrazine, the AUC (0-t) (385.37 ± 93.05 versus 851.64 ± 104.26 lg/L Ã h), t 1/2 (5.46 ± 0.93 versus 6.34 ± 1.25 h), and C max (62.64 ± 9.09 versus 83.87 ± 6.15 lg/L) of valsartan was significantly decreased, and the clearance rate was increased from 10.92 ± 1.521 to 25.76 ± 6.24 L/h/kg and similar changes were observed in the group with 10 mg/kg ligustrazine (p < 0.05). The metabolic stability of valsartan was also decreased by ligustrazine as the half-life of valsartan in rat liver microsomes decreased from 37.12 ± 4.06 to 33.48 ± 3.56 min and the intrinsic clearance rate increased from 37.34 ± 3.84 to 41.40 ± 4.32 lL/min/mg protein (p < 0.05). Discussion and conclusions: Ligustrazine promoted the metabolism of valsartan via activating CYP3A4. The co-administration of ligustrazine and valsartan should be taken into account.

Pharmacokinetic study of the interaction between luteolin and magnoflorine in rats

“…Similarly, the inhibitory effect of anemarsaponin BII on CYP3A4 led to its interaction with nobiletin, an extraction of Citrus reticulata Blanco (Rutaceae) metabolized by CYP3A4 (Zhang et al, 2021). The induction of CYP3A4 by ligustrazine was reported to promote the metabolism of valsartan which reduce the plasma concentration and shorten the exposure of valsartan (Liu et al, 2020). The concentration‐dependent inhibition of CYP3A by magnoflorine was observed in the present study, which is consistent with a previous study (Han et al, 2011).…”

Potential herb–drug interactions between anti-COVID-19 drugs and traditional Chinese medicine

“…Furthermore, the bioactive ingredient of Scutellariae Radix (Baicalin) in QFPD and JHQG could induce the activity of CYP3A4 177 . Ligustrazine, an effective component of Chuanxiong Rhizoma in XBJ, could also induce the activity of CYP3A4 454 , 471 . Tanshinone IIA and cryptotanshinone are the active ingredients of Salvia , an herb in XBJ, which could also induce CYP3A4 activity 460 .…”

The Therapeutic Effects of Ligustrazine in Combination with Other Drugs in Cardiovascular Diseases

“…Valsartan alleviated cardiomyopathy and improved heart function in patients, but the hepatic metabolism of this drug in the body is not ideal [44,45]. Ligustrazine (Chuan Xiong Qin) pretreatment was proved to improve the metabolism of valsartan through activation of the hepatic enzyme Cytochrome P450 3A4 (CYP3A4) in SD rats [16]. The combination of valsartan and ligustrazine (Chuan Xiong Qin) indeed produced a better effect than either of them alone in the inhibition of cerebral ischemiareperfusion-induced free radical formation and hippocampal neuronal loss in rats with vascular dementia [46].…”