title: The effect of 1-furan-2-yl-3-pyridine-2-yl-propenone on pharmacokinetic parameters of theophylline.
abstract: 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.
authors.affiliation: College of Pharmacy, Yeungnam University, Kyungsan, Kyungbuk, Korea.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Shanmugam
authors.forename: Eung Seok
authors.initials: ES
authors.lastname: Lee
authors.forename: Sang Kyu
authors.initials: SK
authors.lastname: Lee
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Jeon
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Bong Kyu
authors.initials: BK
authors.lastname: Yoo
mesh_terms: 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
chemical_list: 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