title: Effect of fermented red ginseng on cytochrome P450 and P-glycoprotein activity in healthy subjects, as evaluated using the cocktail approach.
abstract: We assessed the drug interaction profile of fermented red ginseng with respect to the activity of major cytochrome (CYP) P450 enzymes and of a drug transporter protein, P-glycoprotein (P-gp), in healthy volunteers.
  
  
  
  This study was an open-label crossover study. The CYP probe cocktail drugs caffeine, losartan, dextromethorphan, omeprazole, midazolam and fexofenadine were administered before and after 2 weeks of fermented red ginseng administration. Plasma samples were collected, and tolerability was assessed. Pharmacokinetic parameters were calculated, and the 90% confidence intervals (CIs) of the geometric mean ratios of the parameters were determined from logarithmically transformed data. Values were compared between before and after fermented red ginseng administration using analysis of variance (anova).
  
  
  
  Fifteen healthy male subjects were evaluated, none of whom were genetically defined as a poor CYP2C9, CYP2C19 or CYP2D6 metabolizer based on genotyping. Before and after fermented red ginseng administration, the geometric least-square mean metabolic ratio (90% CI) was 0.901 (0.830-0.979) for caffeine (CYP1A2) to paraxanthine, 0.774 (0.720-0.831) for losartan (CYP2C9) to EXP3174, 1.052 (0.925-1.197) for omeprazole (CYP2C19) to 5-hydroxyomeprazole, 1.150 (0.860-1.538) for dextromethorphan (CYP2D6) to dextrorphan, and 0.816 (0.673-0.990) for midazolam (CYP3A4) to 1-hydroxymidazolam. The geometric mean ratio of the area under the curve of the last sampling time (AUClast) for fexofenadine (P-gp) was 1.322 (1.112-1.571).
  
  
  
  No significantly different drug interactions were observed between fermented red ginseng and the CYP probe substrates following the two-week administration of concentrated fermented red ginseng. However, the inhibition of P-gp was significantly different between fermented red ginseng and the CYP probe substrates. The use of fermented red ginseng requires close attention due to the potential for increased systemic exposure when it is used in combination with P-gp substrate drugs.
authors: Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors: Min-Gul
authors: MG
authors: Kim
authors: Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors: Yunjeong
authors: Y
authors: Kim
authors: Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors: Ji-Young
authors: JY
authors: Jeon
authors: Department of Laboratory Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors: Dal-Sik
authors: DS
authors: Kim
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D002110:Caffeine / Q000008:administration & dosage / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D065729:Cytochrome P-450 CYP2C9 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004347:Drug Interactions; D000074421:Fermented Foods; D064368:Healthy Volunteers; D006801:Humans; D019808:Losartan / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000493:pharmacokinetics; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics; D005894:Panax; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004364:Pharmaceutical Preparations; D002110:Caffeine; D016593:Terfenadine; C093230:fexofenadine; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019808:Losartan; D009853:Omeprazole; D008874:Midazolam
keywords: P-glycoprotein; cytochrome P450; drug interaction; fermented red ginseng