Study on the pharmacokinetics drug-drug interaction potential of Glycyrrhiza uralensis, a traditional Chinese medicine, with lidocaine in rats.
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.
Tang
Jingcheng
J
School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing, China.
Song
Xiaohong
X
Zhu
Min
M
Zhang
Jinnan
J
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics*; D029882:Glycyrrhiza uralensis / Q000737:chemistry*; D041743:Herb-Drug Interactions; D008012:Lidocaine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008516:Medicine, Chinese Traditional; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004365:Drugs, Chinese Herbal; D003577:Cytochrome P-450 Enzyme System; D008012:Lidocaine