Benzydamine N-oxygenation as an index for flavin-containing monooxygenase activity and benzydamine N-demethylation by cytochrome P450 enzymes in liver microsomes from rats, dogs, monkeys, and humans

Drug Metabolism and Pharmacokinetics
Tomomi Taniguchi-TakizawaHiroshi Yamazaki

Abstract

Benzydamine is an anti-inflammatory drug that undergoes flavin-containing monooxygenase (FMO)-dependent metabolism to benzydamine N-oxide; however, benzydamine N-demethylation is also catalyzed by liver microsomes. In this study, benzydamine N-oxygenation and N-demethylation mediated by liver microsomes from rats, dogs, monkeys, and humans were characterized comprehensively. Values of the maximum velocity/Michaelis constant ratio for benzydamine N-oxygenation by liver microsomes from dogs and rats were higher than those from monkeys and humans, despite roughly similar rates of N-demethylation in the four species. Benzydamine N-oxygenation by liver microsomes was extensively suppressed by preheating liver microsomes at 45 °C for 5 min or at 37 °C for 5-10 min without NADPH, and benzydamine N-demethylation was strongly inhibited by 1-aminbobenztriazole. Liver microsomal benzydamine N-oxygenation was inhibited by dimethyl sulfoxide and methimazole, whereas N-demethylation was inhibited by quinidine. High benzydamine N-oxygenation activities of recombinant human FMO1 and FMO3 and human kidney microsomes were observed at pH 8.4, whereas N-demethylation by cytochrome P450 2D6 was faster at pH 7.4. These results suggest that benzydami...Continue Reading

References

Jan 26, 2002·Pediatric Research·Sevasti B KoukouritakiRonald N Hines
Jun 1, 2005·Pharmacology & Therapeutics·Sharon K Krueger, David E Williams
Nov 22, 2005·Pharmacogenomics·Sevasti B Koukouritaki, Ronald N Hines
Jan 13, 2006·Annual Review of Pharmacology and Toxicology·John R Cashman, Jun Zhang
Dec 1, 2011·European Journal of Human Genetics : EJHG·Elizabeth A ShephardIan R Phillips
Dec 20, 2011·Biochemical Pharmacology·Gianluca CatucciSheila J Sadeghi
Apr 30, 2013·Biochemical Pharmacology·Yasuhiro UnoHiroshi Yamazaki
Jul 17, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yoshinobu NakamaruMasayuki Suzuki
Mar 29, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Jaana HartialaUNKNOWN CARDIoGRAM Consortium

❮ Previous
Next ❯

Citations

Mar 18, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Turan GulRainer Bischoff
Feb 2, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Miho Yamazaki-NishiokaHiroshi Yamazaki
Apr 26, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yildiz YilmazGian Camenisch
Aug 19, 2017·The Journal of Pharmacology and Experimental Therapeutics·Meijuan XuBhagwat Prasad
Aug 9, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Barry C JonesDanxi Li
Mar 5, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shotaro UeharaHiroshi Yamazaki
Nov 2, 2018·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Yadira X Perez-ParamoPhilip Lazarus

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.