title: Drug-herb interaction: effect of St John's wort on bioavailability and metabolism of procainamide in mice.
abstract: BACKGROUND
  St John's wort induces the activity of the cytochrome P450 enzyme system causing treatment failure because of increased metabolism of many drugs. Procainamide is metabolized by a different pathway to N-acetyl procainamide.
  
  
  OBJECTIVE
  To study St John's wort-procainamide interaction using a mouse (Swiss Webster) model.
  
  
  METHODS
  One group of mice (group A, 4 mice in each group) was fed St John's wort each day for 2 weeks (last dose 1 day before administration of procainamide); another group (group B) received the same dose of St John's wort for 1 week. The third group (group C) received only a single dose 1 hour before administration of procainamide, and the control group (group D) received no St John's wort. All groups later received a single oral dose of procainamide. Blood was drawn 1, 4, and 24 hours after administration of procainamide and concentrations in serum of procainamide as well as N-acetyl procainamide were measured using immunoassays.
  
  
  RESULTS
  The procainamide concentrations 1 hour after administration was highest in group C (mean, 11.59 microg/mL) followed by group A (9.92 microg/mL), whereas group B (7.44 microg/mL) and control group D (7.36 microg/mL) showed comparable values. The concentration in group C was significantly greater than the control group D (P = .03, 2-tailed independent t test). N-Acetyl procainamide concentrations and estimated half-life of procainamide among groups were comparable. In a separate experiment when mice were fed purified hypericin, the active component of St John's wort, a significant increase in bioavailability (53%) of procainamide was observed compared with the control group.
  
  
  CONCLUSIONS
  St John's wort has an acute effect to increase bioavailability of procainamide but has no effect on its metabolism.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, 6431 Fannin, MSB 2.292, Houston, TX 77030, USA. Amitava.Dasgupta@uth.tmc.edu
authors.forename: Amitava
authors.initials: A
authors.lastname: Dasgupta
authors.forename: Melissa
authors.initials: M
authors.lastname: Hovanetz
authors.forename: Margaret
authors.initials: M
authors.lastname: Olsen
authors.forename: Alice
authors.initials: A
authors.lastname: Wells
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Actor
mesh_terms: D000120:Acecainide / Q000493:pharmacokinetics; D000818:Animals; D000873:Anthracenes; D001682:Biological Availability; D005260:Female; D041743:Herb-Drug Interactions; D020902:Hypericum; D051379:Mice; D010569:Perylene / Q000031:analogs & derivatives / Q000494:pharmacology; D011342:Procainamide / Q000493:pharmacokinetics*
chemical_list: D000873:Anthracenes; D010569:Perylene; C004965:hypericin; D000120:Acecainide; D011342:Procainamide