title: Effects of St. John's wort supplementation on ibuprofen pharmacokinetics.
abstract: BACKGROUND
  St. John's wort is a popular herbal supplement that has been involved in various herb-drug interactions. Experimental findings suggest that the supplement may impact CYP2C9 metabolism. CYP2C9 is responsible for the irreversible metabolism of ibuprofen.
  
  
  OBJECTIVE
  To examine the effect of 3 weeks of St. John's wort administration on the stereoselective pharmacokinetics of ibuprofen.
  
  
  METHODS
  Eight male subjects participated in this study. The single-dose pharmacokinetics of ibuprofen were evaluated before and after 21 days of St. John's wort administration. Plasma ibuprofen concentrations were determined, using a stereoselective, reversed-phase HPLC assay. Model independent methods were used to evaluate the pharmacokinetics of each ibuprofen enantiomer. Data were analyzed by 2 way ANOVA testing and confidence interval testing.
  
  
  RESULTS
  S(+)-ibuprofen mean +/- SD AUC and maximum concentration (C(max)) values were 131.6 +/- 26.8 microg x h/mL and 31.8 +/- 7.33 microg/mL, respectively, for control samples and 122.4 +/- 32.9 microg x h/mL and 33.6 +/- 7.83 microg/mL, respectively, after St. John's wort treatment. R(-)-ibuprofen mean AUC and C(max) values were 85.1 +/- 26.6 microg x h/mL and 28.4 +/- 8.72 microg/mL, respectively, for control samples and 87.7 +/- 30.1 microg x h/mL and 30.0 +/- 8.97 microg/mL, respectively, for St. John's wort treatment samples. St. John's wort administration resulted in no significant effects on the C(max) and AUC of either stereoisomer. A 31% decrease in S(+)-ibuprofen mean residence time (p = 0.02) was observed.
  
  
  CONCLUSIONS
  St. John's wort administration for 21 days had no apparent clinically important impact on the single-dose pharmacokinetic parameters of S(+)- and R(-)-ibuprofen. Although St. John's wort treatment appears to significantly reduce the mean residence time of S-ibuprofen, no ibuprofen dose adjustments appear warranted when the drug is administered orally with St. John's wort, due to the lack of significant change observed in ibuprofen AUC and C(max) for either enantiomer.
authors.affiliation: College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA. bellec@tsu.edu
authors.forename: Edward C
authors.initials: EC
authors.lastname: Bell
authors.forename: William R
authors.initials: WR
authors.lastname: Ravis
authors.forename: Kimberly Braxton
authors.initials: KB
authors.lastname: Lloyd
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Stokes
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D041743:Herb-Drug Interactions; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D007052:Ibuprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D028321:Plant Preparations / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D028321:Plant Preparations; D007052:Ibuprofen