title: Non-Linear Pharmacokinetics of Atomoxetine in Adult Japanese Patients With ADHD.
abstract: Objective:The objective was to reveal the relationship between dose and concentration of atomoxetine.Method:Fifty-five blood samples of 33 patients with ADHD were examined using high-performance liquid chromatography.Results:The plasma concentrations were 53.2 ± 67.0, 298.0 ± 390.5, and 639.3 ± 831.9 ng/mL at doses of 40 mg, 80 mg, and 120 mg, and the concentration/dose were 1.33 ± 1.67, 3.73 ± 4.88, and 5.33 ± 6.93 ng/mL/mg, respectively. Statistical analyses revealed a significant correlation between the concentration and the dose of atomoxetine (p= .004), and a trending toward significance in the difference in the concentration/dose in the three dosage groups (p= .064). The concentration/dose at 40 and 80 + 120 mg/day were 1.33 ± 1.67 and 4.22 ± 5.53 ng/mL/mg, the latter was significantly higher than the former (p= .006), which suggested non-linear pharmacokinetics.Conclusion:Clinicians should carefully titrate in high dose atomoxetine treatment.
authors.affiliation: Niigata University, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Sugimoto
authors.affiliation: Niigata University, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Niigata University, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Orime
authors.affiliation: Niigata University, Japan.
authors.forename: Taketsugu
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Niigata University, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Egawa
authors.affiliation: Niigata University, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Sugai
authors.affiliation: Dokkyo Medical University, Shimotsuga, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Niigata University, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
mesh_terms: D018759:Adrenergic Uptake Inhibitors; D000328:Adult; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007564:Japan; D011437:Propylamines
chemical_list: D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride
keywords: ADHD; adult ADHD; atomoxetine; non-linear kinetics; plasma concentration