Alteration of the pharmacokinetics of theophylline by rutaecarpine, an alkaloid of the medicinal herb Evodia rutaecarpa, in rats.

Abstract

Rutaecarpine is a main active alkaloid present in the medicinal herb, Evodia rutaecarpa. The cytochrome P450 (CYP) 1A2 substrate, theophylline, is an important therapeutic agent for the treatment of asthma, but has a narrow therapeutic index. To evaluate the pharmacokinetic interaction of theophylline with rutaecarpine, the effects of rutaecarpine on CYP1A2 activity and theophylline pharmacokinetics were investigated. Oral treatment of Sprague-Dawley rats with 50 mg kg(-1) rutaecarpine for three days through a gastrogavage caused a 4- and 3-fold increase in liver microsomal 7-ethoxyresorufin O-deethylation (EROD) and 7-methoxyresorufin O-demethylation activity, respectively. In the kidney, rutaecarpine treatment caused a 3-fold increase in EROD activity. In the lungs, EROD activity was elevated from an undetectable to a detectable level by rutaecarpine. Pharmacokinetic parameters of theophylline were determined using a microdialysis sampling method. Rutaecarpine pre-treatment increased the clearance of theophylline in a dose-dependent manner. Pre-treatment of rats with 50 mg kg(-1) rutaecarpine caused a 3-fold increase in theophylline clearance and a 70%, 68% and 68% decrease in the area under the concentration-time curve (AUC), mean residence time (MRT) and half-life, respectively. These results demonstrated that rutaecarpine treatment elevated CYP1A2 catalytic activity and theophylline excretion in rats. In patients taking theophylline, adverse effects might be noticed when a rutaecarpine-containing herbal preparation is used concomitantly.

• Authors: Yune-Fang Ueng, Tung-Hu Tsai, Ming-Jaw Don, Ruei-Ming Chen, Ta-Liang Chen
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 57 Issue 2 Pg. 227-32 (Feb 2005) ISSN: 0022-3573 [Print] England
• PMID: 15720787 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Indole Alkaloids
• Oxazines
• Quinazolines
• 7-methoxyresorufin
• rutecarpine
• Theophylline
• Cytochrome P-450 CYP1A1

Topics

• Alkaloids (administration & dosage, chemistry, isolation & purification, pharmacokinetics, pharmacology)
• Animals
• Area Under Curve
• Cytochrome P-450 CYP1A1 (drug effects, metabolism)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Evaluation, Preclinical (methods)
• Drug Interactions
• Enzyme Induction
• Evodia (chemistry)
• Half-Life
• Indole Alkaloids
• Intubation, Gastrointestinal
• Kidney (chemistry, drug effects, metabolism)
• Lung (chemistry, drug effects, metabolism)
• Male
• Microdialysis (methods)
• Microsomes, Liver (chemistry, drug effects, metabolism)
• Oxazines (metabolism)
• Plants, Medicinal (chemistry)
• Quinazolines
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Theophylline (administration & dosage, blood, pharmacokinetics)
• Time Factors