title: Evaluation of bioequivalence of five 0.1 mg dutasteride capsules compared to one 0.5 mg dutasteride capsule: a randomized study in healthy male volunteers.
abstract: OBJECTIVE
  To evaluate the bioequivalence of five 0.1 mg dutasteride capsules to one 0.5 mg dutasteride capsule in healthy adult male subjects under fasting conditions.
  
  
  METHODS
  This was a single-center, open-label, randomized, single dose, two-way cross-over study (ClinicalTrials.gov identifier NCT01929330). Thirty-six healthy male subjects aged 18-65 years received 5 × 0.1 mg dutasteride softgel capsules and 1 × 0.5 mg dutasteride softgel capsule in a randomized order, with a minimum washout of 28 days between each drug administration. Serial blood samples were collected for the measurement of serum dutasteride concentrations by a validated HPLC-MS/MS method. Dutasteride pharmacokinetic parameters were calculated using non-compartmental analysis. Maximum concentration (Cmax) and area under the concentration-time curve to the last quantifiable concentration (AUC[0-t]) were compared between treatments. Safety and tolerability were monitored throughout the study.
  
  
  RESULTS
  Five 0.1 mg dutasteride capsules were demonstrated to be bioequivalent to 1 × 0.5 mg dutasteride capsule, as the 90% confidence intervals for Cmax and AUC were within the accepted bioequivalence range of 0.80-1.25. The geometric least squares means ratios and associated 90% confidence intervals for 5 × 0.1 mg capsules vs 1 × 0.5 mg capsule were 1.01 (0.97-1.05) for Cmax and 0.91 (0.84-1.00) for AUC(0-t). Adverse events (AEs) were reported for 42% (15/36) and 36% (12/33) of subjects in the 5 × 0.1 mg and 1 × 0.5 mg dosing sessions, respectively. The most frequent AE for both treatments was headache. No subject had a serious AE.
  
  
  CONCLUSIONS
  Five 0.1 mg dutasteride capsules were shown to be bioequivalent to one 0.5 mg dutasteride capsule in healthy adult male subjects under fasted conditions, suggesting that the two dose strengths can be interchanged. Both treatments were generally well tolerated in healthy male subjects.
authors.affiliation: Clinical Pharmacology Modeling and Simulation, Quantitative Sciences, GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fossler
authors.affiliation: Clinical Statistics, Quantitative Sciences, GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Collins
authors.affiliation: Medicines Development (Immuno-Inflammation), Development & Medical Affairs Division, GlaxoSmithKline K.K., Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ino
authors.affiliation: Medicines Development (Immuno-Inflammation), Development & Medical Affairs Division, GlaxoSmithKline K.K., Tokyo, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Sarai
authors.affiliation: Statistics and Programming, Quantitative Sciences, GlaxoSmithKline, Bangalore, India.
authors.forename: Ramiya
authors.initials: R
authors.lastname: Ravindranath
authors.affiliation: Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Chester L
authors.initials: CL
authors.lastname: Bowen
authors.affiliation: Clinical Pharmacology Science and Study Operations, GlaxoSmithKline Australia Pty Ltd, Abbotsford, Victoria, Australia.
authors.forename: Olivia
authors.initials: O
authors.lastname: Burns
keywords: Bioequivalence; Clinical trial; Dutasteride; Male; Pharmacokinetics