title: Bioavailability and bioequivalence of a darunavir 800-mg tablet formulation compared with the 400-mg tablet formulation.
abstract: Once-daily darunavir/ritonavir (800/100 mg), plus other antiretrovirals, is recommended for HIV-1-infected patients. Low therapy adherence is linked with poor outcomes. Pill burden can impact adherence. An 800-mg darunavir tablet would reduce pill burden.
  
  
  OBJECTIVE
  To assess the relative oral bioavailability (NCT01052883) and bioequivalence (NCT01308658) of a darunavir 800-mg tablet vs. 2 × 400-mg tablets.
  
  
  METHODS
  In two phase I, open-label, randomized, crossover, single-center studies, healthy volunteers received once-daily ritonavir (100 mg, days 1 - 5) and a single 800-mg darunavir dose: 2 × 400-mg tablets (reference) or 1 × 800- mg tablet (test) on day 3 and vice versa after a ≥ 7-day wash-out. Each study had fasted (n = 16 (bioavailability); n = 83 (bioequivalence)) and fed panels (n = 16; n = 45, respectively). Pharmacokinetic profiles and tolerability were assessed.
  
  
  RESULTS
  No volunteers discontinued for treatment-related reasons. Least-square mean ratios (test vs. reference) for darunavir maximum plasma concentrations (C(max)), area under the concentration-time curve from zero to infinity (AUC(0-∞)) were: 1.06 and 1.15 (bioavailability), and 1.02 and 1.00 (bioequivalence), respectively (fasted); 0.89 and 0.88 (bioavailability), and 0.96 and 0.98 (bioequivalence), respectively (fed). 90% confidence intervals (CI) were within 80.00 - 125.00%, except bioavailability AUC(0-∞) (fed and fasted conditions). Median time to C(max) was comparable for both formulations. No clinically relevant differences in adverse events or laboratory abnormalities occurred between formulations.
  
  
  CONCLUSIONS
  Bioequivalence was demonstrated for the 800-mg darunavir tablet (fasted and fed conditions). This formulation can reduce pill burden and potentially increase adherence for HIV-1-infected patients in whom once-daily darunavir/ritonavir 800/100 mg is appropriate.
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA, Janssen Research & Development, and Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Kakuda
authors.forename: Lorant
authors.initials: L
authors.lastname: Leopold
authors.forename: Maarten
authors.initials: M
authors.lastname: Timmers
authors.forename: Tom
authors.initials: T
authors.lastname: Van De Casteele
authors.forename: Vera
authors.initials: V
authors.lastname: Hillewaert
authors.forename: Frank L
authors.initials: FL
authors.lastname: Tomaka
authors.forename: Richard M W
authors.initials: RM
authors.lastname: Hoetelmans
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D000069454:Darunavir; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005215:Fasting / Q000097:blood; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D019518:Postprandial Period; D019438:Ritonavir / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D013449:Sulfonamides; D013607:Tablets; D019438:Ritonavir; D000069454:Darunavir