title: Intake of St John's wort improves the glucose tolerance in healthy subjects who ingest metformin compared with metformin alone.
abstract: OBJECTIVE
  Our objective was to investigate the steady-state pharmacokinetic and pharmacodynamic interaction between the antidepressive herbal medicine St John's wort and the antidiabetic drug metformin.
  
  
  METHODS
  We performed an open cross-over study in 20 healthy male subjects, who received 1 g of metformin twice daily for 1 week with and without 21 days of preceding and concomitant treatment with St John's wort. The pharmacokinetics of metformin was determined, and a 2 h oral glucose tolerance test was performed.
  
  
  RESULTS
  St John's wort decreased the renal clearance of metformin but did not affect any other metformin pharmacokinetic parameter. The addition of St John's wort decreased the area under the glucose concentration-time curve [702 (95% confidence interval, 643-761) vs. 629 min*mmol/L (95% confidence interval, 568-690), P = 0.003], and this effect was caused by a statistically significant increase in the acute insulin response.
  
  
  CONCLUSIONS
  St John's wort improves glucose tolerance by enhancing insulin secretion independently of insulin sensitivity in healthy male subjects taking metformin.
authors.affiliation: Research Unit of Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Tore Bjerregaard
authors.initials: TB
authors.lastname: Stage
authors.forename: Rasmus Steen
authors.initials: RS
authors.lastname: Pedersen
authors.forename: Per
authors.initials: P
authors.lastname: Damkier
authors.forename: Mette Marie Hougaard
authors.initials: MM
authors.lastname: Christensen
authors.forename: Søren
authors.initials: S
authors.lastname: Feddersen
authors.forename: John Teilmann
authors.initials: JT
authors.lastname: Larsen
authors.forename: Kurt
authors.initials: K
authors.lastname: Højlund
authors.forename: Kim
authors.initials: K
authors.lastname: Brøsen
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D004347:Drug Interactions; D005951:Glucose Tolerance Test; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D008687:Metformin / Q000493:pharmacokinetics* / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D008687:Metformin
keywords: St John's wort; drug-herb interaction; metformin; pharmacodynamics; pharmacokinetics