Drug-herb interaction: effect of St John's wort on bioavailability and metabolism of procainamide in mice.
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.
Dasgupta
Amitava
A
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
Hovanetz
Melissa
M
Olsen
Margaret
M
Wells
Alice
A
Actor
Jeffrey K
JK
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*
D000873:Anthracenes; D010569:Perylene; C004965:hypericin; D000120:Acecainide; D011342:Procainamide