title: Bioequivalence Studies of a Reformulated Dutasteride and Tamsulosin Hydrochloride Combination Capsule and a Commercially Available Formulation.
abstract: A dutasteride 0.5 mg and tamsulosin hydrochloride 0.4 mg combination (DTC) capsule (Duodart®) was reformulated to reduce the capsule size and enhance product stability. Bioequivalence of the reformulated DTC capsule with the commercial formulation was evaluated in 2 single-dose, open-label, randomized, 2-way crossover studies in healthy adult male volunteers. Subjects in a fasted or fed state received a single oral dose of either the reformulated DTC or the commercial formulation followed by a 28-day washout period between treatments. Blood samples were taken predose and up to 72 hours postdose for pharmacokinetic (PK) analysis of dutasteride and tamsulosin serum concentrations. From the serum concentration-vs-time data, a noncompartmental method was used to calculate the maximum observed serum concentration (Cmax) and area under the serum concentration-time curve (AUC0-t) for dutasteride and tamsulosin, and AUC0-∞for tamsulosin. The 90% confidence intervals for the ratios of the Cmaxand AUC0-t(for dutasteride and tamsulosin) and for AUC0-∞(for tamsulosin) were all completely contained within the range of 80% to 125%; therefore, the reformulated DTC capsule is bioequivalent to the commercial formulation under both fed and fasted states.
authors.affiliation: GlaxoSmithKline Research and Development Projects Clinical Platforms and Sciences, Upper Providence, Collegeville, PA, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Kurczewski
authors.affiliation: GlaxoSmithKline Research and Development Projects Clinical Platforms and Sciences, Upper Merion, King of Prussia, PA, USA.
authors.forename: Chet
authors.initials: C
authors.lastname: Bowen
authors.affiliation: PAREXEL International, Durham, North Carolina.
authors.forename: David
authors.initials: D
authors.lastname: Collins
authors.affiliation: GlaxoSmithKline Research and Development Projects Clinical Platforms and Sciences, Upper Merion, King of Prussia, PA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Incyte Corp, Wilmington, DE, USA.
authors.forename: Gulyeter
authors.initials: G
authors.lastname: Serbest
authors.affiliation: GlaxoSmithKline Research and Development Global Medical Urology, Parque Technologico De Madrid, Tres Cantos, Madrid, Spain.
authors.forename: Michael
authors.initials: M
authors.lastname: Manyak
mesh_terms: D000328:Adult; D002214:Capsules; D018592:Cross-Over Studies; D004338:Drug Combinations; D004339:Drug Compounding / Q000379:methods*; D000068538:Dutasteride / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D011897:Random Allocation; D013449:Sulfonamides / Q000493:pharmacokinetics*; D000077409:Tamsulosin; D013810:Therapeutic Equivalency
chemical_list: D002214:Capsules; D004338:Drug Combinations; D013449:Sulfonamides; D000077409:Tamsulosin; D000068538:Dutasteride
keywords: bioequivalence; dutasteride plus tamsulosin combination; healthy male volunteers; pharmacokinetics; two-way crossover