Potential drug interactions associated with glycyrrhizin and glycyrrhetinic acid

Abstract

Glycyrrhizin (GZ), the main active component of licorice, is a widely used therapeutic in the clinic. Depending on the disease, the treatment may involve a long course of high dose GZ. Another component of licorice, glycyrrhetinic acid (GA), is the main active metabolite of GZ and is thought to be responsible for the majority of the pharmacological properties of GZ. Therefore, GZ and GA are both used for therapeutic purposes. In addition, GZ and GA are also widely used to sweeten and flavor foods. Due to this widespread, multifaceted use of these substances, potential drug interactions with GZ and GA have recently gained attention. Along these lines, this review covers the known effects of GZ and GA on drug-metabolizing enzymes and efflux transporters. We conclude that both GZ and GA may have an effect on the activity of CYPs. For example, GZ may induce CYP3A activity through activation of PXR. Also, GZ and GA may affect glucuronidation in rats and humans. Furthermore, 18β-GA is a potent inhibitor of P-gp, while GZ and GA are inhibitors of MRP1, MRP2 and BCRP. The pharmacokinetics and pharmacodynamics of many medications may be altered when used concurrently with GZ or GA, which is also covered in this review. Overall, GZ, GA or related products should be taken with caution when taken with additional medications due to the possible drug interactions.

Glycyrrhizin has a high likelihood to be a victim of drug–drug interactions mediated by hepatic organic anion‐transporting polypeptide 1B1/1B3

“…This will help to ensure pharmacokinetic compatibility for the success of glycyrrhizin‐including multidrug treatment of liver diseases. Glycyrrhizin‐related potential drug–drug interactions were recently reviewed (Feng et al ., ; Zhang et al ., ; Wu et al ., ). The reported interactions involved glycyrrhizin as an inducer of cytochrome P450 3A4 (CYP3A4) in human subjects given p.o.…”

Effect of glycyrrhizic acid on rhein renal penetration: a microdialysis study in rats

“…In the present study, the influence of GA on RH renal penetration was investigated to help determine underlying mechanisms regarding the increase in efficacy observed following co-administration (Feng et al, 2015;Sheng et al, 1994). Because accumulation of agents in the interstitial fluid is responsible for their pharmacological responses, a microdialysis technique was used to evaluate the renal penetration of RH.…”

How impaired efficacy happened between Gancao and Yuanhua: Compounds, targets and pathways

“…Among the pathways, mainly two aspects stand out- several tumors and metabolism pathways. As for metabolism, GC’s influence on cytochrome P450 enzymes (CYPs) have drawn attentions from scientists 46 . And for tumors, according to Fig.…”