title: The pregnane X receptor agonist St John's Wort has no effects on the pharmacokinetics and pharmacodynamics of repaglinide.
abstract: OBJECTIVE
  St John's wort (SJW; Hypericum perforatum) has been one of the most commonly used herbal remedies for mood disorders. This study aimed to investigate the effect of SJW, a pregnane X receptor (PXR) agonist, on the pharmacokinetics and pharmacodynamics of repaglinide, a widely consumed glucose-lowering drug.
  
  
  METHODS
  In a two-phase, randomized, crossover study with a 4-week washout period between phases, 15 healthy subjects with specific solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes were given pretreatment with SJW 325 mg or placebo three times daily for 14 days, and a single dose of repaglinide 1 mg was administered followed by 75 g glucose at 15 minutes after repaglinide administration.
  
  
  RESULTS
  In all subjects, SJW had no effect on the total area under the plasma concentration-time curve from time zero to infinity (AUC(∞)), the peak plasma concentration (C(max)) or the elimination half-life (t(&frac12;)) of repaglinide. In addition, SJW had no significant effect on the blood glucose-lowering and insulin-elevating effects of repaglinide.
  
  
  CONCLUSIONS
  Consumption of SJW for 14 days had no clinically significant effect on the pharmacokinetics and pharmacodynamics of repaglinide.
authors.affiliation: Hunan Key Laboratory of Pharmacogenetics, Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Fan
authors.forename: Gan
authors.initials: G
authors.lastname: Zhou
authors.forename: Dong
authors.initials: D
authors.lastname: Guo
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Liu
authors.forename: Wang-Qing
authors.initials: WQ
authors.lastname: Chen
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Tan
authors.forename: Deng
authors.initials: D
authors.lastname: Sheng
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D002219:Carbamates / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D018592:Cross-Over Studies; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003863:Depression / Q000188:drug therapy*; D005838:Genotype; D041743:Herb-Drug Interactions / Q000235:genetics*; D006801:Humans; D020902:Hypericum; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters / Q000235:genetics; D008517:Phytotherapy; D010880:Piperidines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D010919:Placebos; D010936:Plant Extracts / Q000493:pharmacokinetics* / Q000494:pharmacology; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D002219:Carbamates; D007004:Hypoglycemic Agents; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D010880:Piperidines; D010919:Placebos; D010936:Plant Extracts; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C503999:SLCO1B1 protein, human; C072379:repaglinide; D003577:Cytochrome P-450 Enzyme System