title: Lack of effect of St John's Wort on carbamazepine pharmacokinetics in healthy volunteers.
abstract: BACKGROUND
  St John's Wort is a popular herbal product used by approximately 7% of patients with epilepsy. Previous reports have described reductions in concentrations of CYP3A4 substrates indinavir and cyclosporine (INN, ciclosporin) associated with St John's Wort.
  
  
  OBJECTIVE
  Our objective was to determine the effect of St John's Wort on steady state carbamazepine and carbamazepine-10,11-epoxide pharmacokinetics.
  
  
  METHODS
  Eight healthy volunteers (5 men; age range, 24-43 years) participated in this unblinded study. Subjects received 100 mg of carbamazepine twice daily for 3 days, 200 mg twice daily for 3 days, and then 400 mg once daily for 14 days. Blood samples were collected before and 1, 2, 4, 6, 8, 10, 12, and 24 hours after the dose on day 21. The subjects then took 300 mg of St John's Wort (0.3% hypericin standardized tablet) 3 times daily with meals and with carbamazepine for 14 days. On day 35, blood sampling was repeated. Plasma samples were analyzed for carbamazepine and carbamazepine-10,11-epoxide with HPLC. We compared carbamazepine and carbamazepine-10,11-epoxide noncompartmental pharmacokinetic parameter values before and after St John's Wort with a paired Student t test.
  
  
  RESULTS
  We found no significant differences before or after the administration of St John's Wort in carbamazepine peak concentration (7.2 +/- 1 mg/L before versus 7.6 +/- 1.3 mg/L after), trough concentration (4.8 +/- 0.5 mg/L before versus 4.3 +/- 0.8 mg/L after), area under the plasma concentration-time curve (142.4 +/- 12.9 mg x h/L before versus 143.8 +/- 27.2 mg x h/L after), or oral clearance (2.8 +/- 0.3 L/h before versus 2.9 +/- 0.6 L/h after). Similarly, no differences were found in peak concentration (2 +/- 0.5 mg/L before versus 2.1 +/- 0.4 mg/L after), trough concentration (1.3 +/- 0.3 mg/L before versus 1.4 +/- 0.3 mg/L after), and area under the plasma concentration-time curve (37.5 +/- 7.4 mg x h/L before versus 41.9 +/- 10.3 mg x h/L after) of carbamazepine-10,11-epoxide.
  
  
  CONCLUSIONS
  The results suggest that treatment with St John's Wort for 14 days did not further induce the clearance of carbamazepine.
authors.affiliation: Clinical Center Pharmacy Department, Epilepsy Research Branch, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. aburstein@nih.gov
authors.forename: A H
authors.initials: AH
authors.lastname: Burstein
authors.forename: R L
authors.initials: RL
authors.lastname: Horton
authors.forename: T
authors.initials: T
authors.lastname: Dunn
authors.forename: R M
authors.initials: RM
authors.lastname: Alfaro
authors.forename: S C
authors.initials: SC
authors.lastname: Piscitelli
authors.forename: W
authors.initials: W
authors.lastname: Theodore
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D020902:Hypericum / Q000009:adverse effects*; D008297:Male; D010946:Plants, Medicinal
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; C012227:carbamazepine epoxide