title: Pharmacokinetics of darunavir after administration of an oral suspension with low-dose ritonavir and with or without food.
abstract: This 2-part, phase 1, open-label, randomized, crossover study (NCT00752310) assessed ritonavir-boosted darunavir bioavailability (oral suspension vs. tablets), and steady-state darunavir pharmacokinetics (suspension). Part 1: 20 healthy adults randomly received 3 treatments with a ≥7-day washout between treatments; twice-daily ritonavir (100 mg, days 1-5) with darunavir (600 mg, day 3) as 2 × 300-mg tablets (fed, reference), or 6 mL of a 100-mg/mL suspension (fed or fasted, test). Part 2: 18 healthy volunteers received twice-daily darunavir (suspension, 600 mg days 1-6, one dose day 7) with twice-daily ritonavir (100 mg, days 1-9). Darunavir pharmacokinetics were evaluated (part 1 day 3; part 2 day 7). Safety/tolerability were assessed. In part 1, 90% confidence intervals for darunavir Cmax and AUC were all within 80-125% for suspension (fed or fasted) versus tablets (fed). Steady-state darunavir (suspension) pharmacokinetics in part 2 were similar to historic controls (tablets). No clinically relevant differences in adverse events or laboratory abnormalities occurred between treatments. Darunavir administered as an oral suspension or tablets (both with low-dose ritonavir) showed comparable bioavailability in healthy adults after a single dose. Steady-state darunavir pharmacokinetics (suspension, 600/100 mg twice daily) were consistent with historic controls; this formulation is considered suitable for pediatric use and for adults who cannot swallow tablets.
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA.
authors.forename: Thomas N
authors.identifier: 0000-0001-6857-2572
authors.initials: TN
authors.lastname: Kakuda
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA.
authors.forename: Vanitha
authors.initials: V
authors.lastname: Sekar
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Ludo
authors.initials: L
authors.lastname: Lavreys
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: De Paepe
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Tanja
authors.initials: T
authors.lastname: Stevens
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Vanstockem
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Tony
authors.initials: T
authors.lastname: Vangeneugden
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Richard M W
authors.initials: RM
authors.lastname: Hoetelmans
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D000069454:Darunavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005215:Fasting / Q000097:blood; D005260:Female; D018565:Food-Drug Interactions; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009426:Netherlands; D019999:Pharmaceutical Solutions; D019518:Postprandial Period; D019438:Ritonavir / Q000008:administration & dosage*; D013607:Tablets; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D019999:Pharmaceutical Solutions; D013607:Tablets; D019438:Ritonavir; D000069454:Darunavir
keywords: HIV protease inhibitor; bioavailability; darunavir; pharmacokinetics