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Pharmacokinetics of darunavir after administration of an oral suspension with low‐dose ritonavir and with or without food
Author(s) -
Kakuda Thomas N.,
Sekar Vanitha,
Lavreys Ludo,
De Paepe Els,
Stevens Tanja,
Vanstockem Marc,
Vangeneugden Tony,
Hoetelmans Richard M.W.
Publication year - 2014
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.88
Subject(s) - darunavir , pharmacokinetics , medicine , ritonavir , cmax , bioavailability , crossover study , tolerability , pharmacology , adverse effect , viral load , human immunodeficiency virus (hiv) , virology , alternative medicine , pathology , antiretroviral therapy , placebo
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 C max 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.