title: A Phase 1, randomized, open-label crossover study to evaluate the safety and pharmacokinetics of 400 mg albaconazole administered to healthy participants as a tablet formulation versus a capsule formulation.
abstract: BACKGROUND
  Albaconazole is a novel triazole being developed for the oral treatment of fungal diseases. Once-weekly oral dosing with 400 mg albaconazole for 24 or 36 weeks resulted in high rates of clinical and mycological resolution for distal subungual onychomycosis, as well as a favorable safety and tolerability profile.
  
  
  OBJECTIVE
  To compare four 100-mg albaconazole capsules to one 400-mg albaconazole tablet for bioavailability, bioequivalence, tolerability, and safety.
  
  
  METHODS
  Forty participants were enrolled in this Phase I, open-label, two-sequence crossover study. Twenty participants were exposed to a single 400-mg tablet dose of albaconazole before being crossed over to a single dose of four 100-mg albaconazole capsules. The second group of 20 participants received the study products in reverse order. Blood samples were taken over 15 days post-dose to assess the plasma concentrations and pharmacokinetic parameters of albaconazole and its primary metabolite, 6-hydroxyalbaconazole. Safety was assessed throughout the study.
  
  
  RESULTS
  The area under the curve (AUC) and maximum measured plasma concentration (C(max)) of the albaconazole tablet were approximately 10% and 22% lower, respectively, than for the albaconazole capsules. Statistical significance was reached for the C(max) but not for the AUC measurements (AUC(0-t) and AUC(0-inf)). Because the 90% confidence intervals based on the differences between the tablet and capsule were outside the 80%-125% range for both the C(max) and AUC, we concluded that the formulations were not bioequivalent with respect to the rate or extent of absorption. Both formulations were safe and well-tolerated in this study. All adverse events (AEs) were generally mild and were mainly gastrointestinal- or nervous system-related (eg, dizziness, headache). No electrocardiogram findings were reported as an AE, and no serious AEs or deaths were reported.
  
  
  CONCLUSIONS
  The AUC and C(max) of albaconazole after a single 400-mg oral dose administered as a tablet formulation were lower than those of a capsule formulation. Albaconazole tablets and capsules cannot, therefore, be considered bioequivalent.
authors: Stiefel, Research Triangle Park, NC, USA.
authors: Koen
authors: K
authors: van Rossem
authors: Jenny A
authors: JA
authors: Lowe
keywords: albaconazole; onychomycosis; pharmacokinetics; triazole
references: Antimicrob Agents Chemother. 2001 Sep;45(9):2524-8
references: 11502524
references: J Antimicrob Chemother. 1999 Aug;44(2):151-62
references: 10473222
references: N Engl J Med. 2009 May 14;360(20):2108-16
references: 19439745
references: Antimicrob Agents Chemother. 2003 Jul;47(7):2342-4
references: 12821494
references: Arch Dermatol. 2002 Mar;138(3):353-7
references: 11902986
references: J Antimicrob Chemother. 1999 Aug;44(2):283-6
references: 10473237
references: Am Fam Physician. 2001 Feb 15;63(4):663-72, 677-8
references: 11237081
references: Ther Clin Risk Manag. 2005 Dec;1(4):299-306
references: 18360572
references: Br J Dermatol. 2003 Mar;148(3):402-10
references: 12653730