title: Pharmacokinetic Profile and Palatability of Atomoxetine Oral Solution in Healthy Japanese Male Adults.
abstract: OBJECTIVE
  There is a clinical need for a liquid formulation of atomoxetine. We assessed the safety and bioequivalence of an atomoxetine oral solution.
  
  
  METHODS
  This was an open-label, randomized, crossover study. Healthy adult male Japanese subjects (n = 42) with a cytochrome P450 2D6 extensive (including intermediate and ultrarapid) metabolizer genotype were administered atomoxetine 50 mg as oral solution and capsules once each, with a washout period >5 days between doses. Blood samples were used to analyze pharmacokinetic parameters, particularly maximum observed drug concentration (Cmax) and area under the concentration vs. time curve from time zero to the last time point with a measurable concentration (AUC0-last). Bioequivalence was concluded if the 90 % confidence interval of the ratio of geometric means between formulations for both Cmaxand AUC0-lastwere within the interval of 0.8-1.25. Safety assessments included determination of adverse events. Taste was evaluated via a five-item questionnaire immediately and 10 min after taking atomoxetine oral solution.
  
  
  RESULTS
  Forty subjects completed the study. Plasma concentration-time profiles of atomoxetine oral solution and capsules were similar, and the statistical analysis of systemic exposure showed that the two formulations were bioequivalent. Adverse events were mild and similar in type and frequency between the formulations. For taste acceptability, only 7.1 % of subjects responded that the oral solution would be difficult to take every day.
  
  
  CONCLUSIONS
  Atomoxetine oral solution is bioequivalent to atomoxetine capsules and potentially fulfills the need for an oral solution atomoxetine formulation that will facilitate treatment of children with attention-deficit hyperactivity disorder.
authors.affiliation: Lilly Research Laboratories Japan, Eli Lilly Japan K.K., 7-1-5 Isogamidori, Chuo-ku, Kobe, Hyogo, 651-0086, Japan. nakano_masako@lilly.com.
authors.forename: Masako
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Witcher
authors.affiliation: Lilly Research Laboratories Japan, Eli Lilly Japan K.K., 7-1-5 Isogamidori, Chuo-ku, Kobe, Hyogo, 651-0086, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Satoi
authors.affiliation: Lilly Research Laboratories Japan, Eli Lilly Japan K.K., 7-1-5 Isogamidori, Chuo-ku, Kobe, Hyogo, 651-0086, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Goto
mesh_terms: D000328:Adult; D000069445:Atomoxetine Hydrochloride / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D002214:Capsules; D000069445:Atomoxetine Hydrochloride