The effect of 1-furan-2-yl-3-pyridine-2-yl-propenone on pharmacokinetic parameters of theophylline.
The pharmacokinetic parameters of theophylline in rats did not change significantly when the drug was intravenously administered after three consecutive days of pretreatment with 17 mg/kg, orally, of 1-furan-2-yl-3-pyridine-2-yl-propenone (FPP-3), an investigatory drug having dual inhibitory action on cyclooxygenase (COX) and 5-lipoxygenase (5-LOX). However, significant changes were found in the pharmacokinetic parameters of the drug at doses of 34 mg/kg and more of FPP-3. Results of cytochrome P450 activity test indicated that the alteration in pharmacokinetic parameters of the drug appears to be due to the inhibitory effect of FPP-3 on cytochrome P450 1A which is responsible for the metabolism of theophylline. Methoxyresorufin-O-demethylase (MROD) and ethoxyresorufin-O-deethylase (EROD) activity assays revealed that the relative activities of cytochrome P450 1A1 and 1A2 were dose-dependently reduced in the presence of 1, 5, and 10 microM FPP-3 concentrations. Taking into consideration that FPP-3 is intended to be primarily used by geriatric patients with chronic diseases and therefore may be used in long-term basis, the investigatory drug needs to be assessed thoroughly in terms of drug interaction with other commonly prescribed medications.
Shanmugam
Srinivasan
S
College of Pharmacy, Yeungnam University, Kyungsan, Kyungbuk, Korea.
Lee
Eung Seok
ES
Lee
Sang Kyu
SK
Jeon
Tae Won
TW
Yong
Chul Soon
CS
Yoo
Bong Kyu
BK
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005663:Furans / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D011407:Propane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011725:Pyridines / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
C508534:1-furan-2-yl-3-pyridin-2-yl-propenone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005663:Furans; D011725:Pyridines; D003577:Cytochrome P-450 Enzyme System; D013806:Theophylline; D011407:Propane