title: Different effects of the selective serotonin reuptake inhibitors fluvoxamine, paroxetine, and sertraline on the pharmacokinetics of fexofenadine in healthy volunteers.
abstract: Although the interaction between selective serotonin reuptake inhibitors (SSRIs) and other drugs is important in the treatment of depression, there have been few studies of SSRIs concerning transporter-mediated interactions in humans. The objective of this study was to evaluate the in vivo effects of commonly used SSRIs on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate.Twelve healthy volunteers (3 females and 9 males) were enrolled in this study. Each subject received a 60-mg dose of fexofenadine orally at baseline. Afterward, they were randomly assigned to receive 3 treatments with a 60-mg dose of fexofenadine after a 7-day treatment with fluvoxamine (50 mg/d), paroxetine (20 mg/d), or sertraline (50 mg/d), with 2-week intervals between the agents.Fluvoxamine pretreatment significantly increased the maximum plasma concentration, the area under the concentration time curves, and the 24-hour urinary fexofenadine excretion by 66% (P = 0.004), 78% (P = 0.029), and 78% (P < 0.001), respectively, without prolonging its elimination half-life. Paroxetine extended the elimination half-life of fexofenadine by 45% (P = 0.042), and it increased the 24-hour urinary fexofenadine excretion by 55% (P = 0.002). Sertraline did not alter any of the pharmacokinetic parameters of fexofenadine.This is the first report of the different effects of 3 commonly used SSRIs on fexofenadine pharmacokinetics in humans. Our 7-day, repeated-dose clinical study in healthy volunteers indicates that fluvoxamine and paroxetine, but not sertraline, may impact the patient exposure to fexofenadine, which is likely the result of P-glycoprotein inhibition in the small intestine and/or the liver.
authors.affiliation: Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan. junsaru@gpo.kumamoto-u.ac.jp
authors.forename: Junji
authors.initials: J
authors.lastname: Saruwatari
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Akamine
authors.forename: Ayaka
authors.initials: A
authors.lastname: Takashima
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Uno
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D016666:Fluvoxamine / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D017374:Paroxetine / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D020280:Sertraline / Q000494:pharmacology*; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016666:Fluvoxamine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D016593:Terfenadine; C093230:fexofenadine