title: Pharmacokinetics and distribution of fluvoxamine to the brain in rats under oxidative stress.
abstract: The effects of oxidative stress (OS) on the pharmacokinetics of fluvoxamine (FLV), particularly on FLV distribution in the plasma, were studied in ferric-nitrilotriacetate-induced OS rat models (OS rats). The study protocol involved a continuous FLV infusion (25.0 μg/kg/min). The resulting mean plasma FLV concentration measured in steady state OS rats was 0.13 ± 0.01 μg/mL, which was significantly lower than plasma concentrations measured in control rats (0.19 ± 0.01 μg/mL). Moreover, the mean FLV concentration in the OS rat brain (0.51 ± 0.08 μg/g) was determined to be approximately half the concentration in control rat brains (0.95 ± 0.11 μg/g). The FLV concentrations in both the unbound fraction of plasma and erythrocytes of OS rats were significantly greater than that of control rats. These results suggest the potential attenuation of FLV's pharmacological effects in patients under OS.
authors.affiliation: Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan. ky05122@poppy.kyoto-phu.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Kobuchi
authors.forename: Keizo
authors.initials: K
authors.lastname: Fukushima
authors.forename: Yukako
authors.initials: Y
authors.lastname: Ito
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sugioka
authors.forename: Kanji
authors.initials: K
authors.lastname: Takada
mesh_terms: D000818:Animals; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005290:Ferric Compounds / Q000008:administration & dosage; D016666:Fluvoxamine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009571:Nitrilotriacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D018384:Oxidative Stress; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D005290:Ferric Compounds; D016666:Fluvoxamine; D009571:Nitrilotriacetic Acid; D017382:Reactive Oxygen Species; D017367:Selective Serotonin Reuptake Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; C020326:ferric nitrilotriacetate