title: St John's wort greatly reduces the concentrations of oral oxycodone.
abstract: BACKGROUND
  Chronic pain is associated with depression. Self-treatment of depression with herbal over-the-counter medicine St John's wort makes pain patients prone to drug interactions.
  
  
  OBJECTIVE
  The aim of this study was to assess the potential of St John's wort to alter the CYP3A-mediated metabolism of a mu-opioid receptor agonist, oxycodone.
  
  
  METHODS
  The study design was placebo-controlled, randomized, cross-over with two phases at intervals of 4 weeks and was conducted with 12 healthy participants. St John's wort (Jarsin) or placebo was administered t.i.d. for 15 days and oral oxycodone hydrochloride 15 mg on day 14. Oxycodone pharmacokinetics and pharmacodynamics were compared after St John's wort or placebo. Behavioural and analgesic effects were assessed with subjective visual analogue scales and cold pressor test. Plasma drug concentrations were measured from 0 to 48 h, behavioural and analgesic effects from 0 to 12 h.
  
  
  RESULTS
  Following St John's wort administration the oxycodone AUC decreased 50% (p<0.001). Oxycodone elimination half-life shortened from a mean+/-SD 3.8+/-0.7 to 3.0+/-0.4h (p<0.001). The self-reported drug effect of oxycodone as measured by AUEC(0-12) decreased significantly (p=0.004). Differences between St John's wort and placebo phases in cold pain threshold and intensity AUEC(0-12) were not observed.
  
  
  CONCLUSIONS
  St John's wort greatly reduced the plasma concentrations of oral oxycodone. The self-reported drug effect of oxycodone decreased significantly. This interaction may potentially be of some clinical significance when treating patients with chronic pain.
authors.affiliation: Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University Hospital and University of Turku, Turku, Finland. tuija.nieminen@utu.fi
authors.forename: Tuija H
authors.initials: TH
authors.lastname: Nieminen
authors.forename: Nora M
authors.initials: NM
authors.lastname: Hagelberg
authors.forename: Teijo I
authors.initials: TI
authors.lastname: Saari
authors.forename: Mikko
authors.initials: M
authors.lastname: Neuvonen
authors.forename: Kari
authors.initials: K
authors.lastname: Laine
authors.forename: Pertti J
authors.initials: PJ
authors.lastname: Neuvonen
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Olkkola
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D005260:Female; D041743:Herb-Drug Interactions; D006801:Humans; D020902:Hypericum; D008297:Male; D010098:Oxycodone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017288:Pain Threshold / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; D010936:Plant Extracts; D010098:Oxycodone