Grepafloxacin (1-cyclopropyl-1,4-dihydro-6-fluoro-5-methyl-7-(3-methyl-1-piperazinyl )-4-oxo-3-quinoline-carboxylic acid, OPC-17116) (1) exhibits potent and broad-spectrum in vitro and in vivo antibacterial activity. In order to identify the structures of the metabolites of grepafloxacin, 17 possible metabolites were prepared. Among them, 6 compounds were found to be actual metabolites (2a, b, 4a, b and 6a, b) of grepafloxacin in rats, dogs and/or humans. The antibacterial activities of these metabolites were found to be weaker than that of grepafloxacin.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1248/cpb.43.2246 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Reactive metabolite of trovafloxacin activates inflammasomes: Implications for trovafloxacin-induced liver injury.
J Appl Toxicol
June 2024
Department of Pharmacotherapeutics and Toxicology, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Osaka, Japan.
Trovafloxacin is a quinolone antibiotic drug with broad-spectrum activity, which was withdrawn from a global market relatively soon after approval because of serious liver injury. The characteristics of trovafloxacin-induced liver injury are consistent with an idiosyncratic reaction; however, the details of the mechanism have not been elucidated. We examined whether trovafloxacin induces the release of damage-associated molecular patterns (DAMPs) that activate inflammasomes.
View Article and Find Full Text PDFFluoroquinolone efflux mediated by ABC transporters.
J Pharm Sci
September 2008
Department of Biomedical Sciences, Physiology, University of Leon, Campus de Vegazana s/n, 24071 Leon, Spain.
Quinolones and fluoroquinolones are broad spectrum bactericidal drugs, which are widely used in both human and veterinary medicine. These drugs can quite easily enter cells and are often used to treat intracellular pathogens. Some fluoroquinolones have been reported to undergo efflux, which could explain their low bioavailability.
View Article and Find Full Text PDFMDR- and CYP3A4-mediated drug-drug interactions.
J Neuroimmune Pharmacol
September 2006
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005 Rockhill Road, Kansas City, MO 64110-2499, USA.
P-glycoprotein (P-gp), multiple drug resistance associated proteins (MRPs), and cytochrome P450 3A4 together constitute a highly efficient barrier for many orally absorbed drugs. Multidrug regimens and corresponding drug-drug interactions are known to cause many adverse drug reactions and treatment failures. Available literature, clinical reports, and in vitro studies from our laboratory indicate that many drugs are substrates for both P-gp and CYP3A4.
View Article and Find Full Text PDFUptake of irinotecan metabolite SN-38 by the human intestinal cell line Caco-2.
Cancer Chemother Pharmacol
May 2005
Department of Pharmacy, Sapporo Social Insurance General Hospital, Chuo 2-jo, 6-chome, Atsubetsu-ku, Sapporo 004-8618, Japan.
Purpose: The aim of this study was to investigate the transport mechanisms of transporters that contribute to the intestinal uptake of 7-ethyl-10-hydroxycamptothecin (SN-38).
Methods: Human intestinal epithelial Caco-2 cells were used to investigate the mechanistic basis of transepithelial uptake of SN-38. We investigated the characteristics of SN-38 uptake into Caco-2 cells.
[Studies on the efficient syntheses of the drug metabolites].
Yakugaku Zasshi
November 2000
Medicinal Chemistry Research Institute, Otsuka Pharmaceutical Co., Ltd., 463-10, Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
This review summarizes our recent findings in the syntheses of drug metabolites. The metabolites of Grepafloxacin (1) and OPC-14117 (10) were prepared from the common intermediates (5) and (21), respectively. Moreover, treatment of 10 with a model P450 system led to a benzyl alcohol derivative (11) in one step.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!