title: Effect of glycyrrhizin on the activity of CYP3A enzyme in humans.
abstract: BACKGROUND
  Glycyrrhizin is a major ingredient of licorice which is widely used in the treatment of various diseases such as chronic hepatitis. Licorice or glycyrrhizin has been shown to alter the activity of CYP3A in rodents. The influence of glycyrrhizin on CYP3A has not been elucidated in humans.
  
  
  OBJECTIVE
  To investigate the effects of repeated glycyrrhizin ingestion on the oral pharmacokinetics of midazolam, a probe drug for CYP3A activity in humans.
  
  
  METHODS
  Sixteen healthy adult male subjects were enrolled in a two-phase randomized crossover design. In each phase the volunteers received placebo or glycyrrhizin for 14 days. On the 15th day, midazolam was administered and blood samples were obtained to determine midazolam plasma concentrations. Bioequivalence was assessed by determining geometric mean ratios (GMRs) and 90% confidence intervals (90% CI).
  
  
  RESULTS
  The geometric mean (geometric coefficient of variation) for the AUC(0-infinity) of midazolam in the placebo group was 196.4 ng x h/ml (30.3%) and after glycyrrhizin treatment, 151.3 ng x h/ml (34.7%). The GMRs and 90% CI for AUC(0-infinity) and Cmax of midazolam in the presence/ absence of glycyrrhizin were 0.77 (0.70, 0.89) and 0.83 (0.74, 1.01), respectively. The 90% CI for AUC(0-infinity) and Cmax for the GMR of glycyrrhizin over placebo were both out of the no-effect boundaries of 0.80-1.25.
  
  
  CONCLUSIONS
  Administration of glycyrrhizin resulted in a modest induction of CYP3A that was clinically relevant according to the bioequivalence analysis.
authors.affiliation: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, 110 Xiang-Ya Road, Changsha, Hunan 410078, People's Republic of China
authors.forename: Jiang-Hua
authors.initials: JH
authors.lastname: Tu
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: He
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.forename: Lan
authors.initials: L
authors.lastname: Fan
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Tan
authors.forename: Yuan-Fei
authors.initials: YF
authors.lastname: Huang
authors.forename: Dong
authors.initials: D
authors.lastname: Guo
authors.forename: Dong-Li
authors.initials: DL
authors.lastname: Hu
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.lastname: Hong-Hao Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004311:Double-Blind Method; D019695:Glycyrrhizic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics*; D015394:Molecular Structure; D013810:Therapeutic Equivalency
chemical_list: D000893:Anti-Inflammatory Agents; D019695:Glycyrrhizic Acid; D051544:Cytochrome P-450 CYP3A; D008874:Midazolam
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