Study on the pharmacokinetics drug–drug interaction potential of glycyrrhiza uralensis, a traditional Chinese medicine, with lidocaine in rats

Abstract Drug–drug interaction potentials of an herbal medicine named Glycyrrhiza uralensis was investigated in rats via in vitro and in vivo pharmacokinetic studies. P 450 levels and the metabolic rate of lidocaine in the liver microsomes prepared from different treatment groups were measured. In a separate in vivo pharmacokinetic study, the pharmacokinetic parameters of lidocaine in plasma and urine were estimated. P 450 levels in the rats pretreated by Glycyrrhiza uralensis were significant higher than that in the non‐treatment control. The increase in P 450 levels was dose‐dependent. Glycyrrhiza uralensis (1 and 3 g/kg) increased P 450 levels by 62% and 91%, respectively, compared with the non‐treatment control (0.695 nmol/mg protein). The metabolic rate of lidocaine in the liver microsomes was significantly higher in the herb pretreated rats. The pharmacokinetic profile of lidocaine was significantly modified in the rats with the herbal pretreatment. Elimination half‐lives were shortened by 39%, and total clearances were increased by 59% with the pretreatment of Glycyrrhiza uralensis . In conclusion, Glycyrrhiza uralensis showed induction effect on P 450 isozymes. Efficacy and safety profiles of a drug may be affected when the herbal products or herbal prescriptions containing the plant medicine were concomitantly used. Copyright © 2009 John Wiley & Sons, Ltd.