PMID- 24964392
OWN - NLM
STAT- MEDLINE
DCOM- 20150805
LR  - 20220331
IS  - 2040-2058 (Electronic)
IS  - 1359-6535 (Linking)
VI  - 19
IP  - 6
DP  - 2014
TI  - Bioequivalence of a darunavir/cobicistat fixed-dose combination tablet versus 
      single agents and food effect in healthy volunteers.
PG  - 597-606
LID - 10.3851/IMP2814 [doi]
AB  - BACKGROUND: Darunavir requires pharmacokinetic enhancement to increase its 
      bioavailability. Cobicistat is potentially an alternative pharmacokinetic booster 
      to ritonavir. Bioequivalence of a darunavir/cobicistat fixed-dose combination 
      (FDC) versus darunavir and cobicistat co-administered as single agents and the 
      effect of a high-fat meal on the pharmacokinetics of the FDC were evaluated. 
      METHODS: In this Phase I, open-label, randomized, three-panel, crossover study 
      (NCT01619527), healthy volunteers received a single dose of darunavir (800 mg) 
      with cobicistat (150 mg) as either an FDC or as single agents co-administered 
      under fasted (panel 1, n=74) or fed (breakfast, panel 2, n=40) conditions, or as 
      the FDC under fasted versus fed (high-fat breakfast) conditions (panel 3, n=19), 
      with a >/=7 day washout period between treatments. Pharmacokinetic profiles, safety 
      and tolerability were assessed. RESULTS: 90% confidence intervals of the least 
      square mean ratios for darunavir and cobicistat maximum plasma concentration and 
      area under the plasma concentration-time curve (AUC) were all within 80.00% and 
      125.00% in panels 1 and 2. Administration of the FDC with a high-fat breakfast 
      significantly increased darunavir maximum plasma concentration 2.27-fold and AUC 
      1.63-1.70-fold, whereas cobicistat pharmacokinetics were unaffected. No 
      volunteers discontinued due to adverse events (AEs). All AEs were grade 1 or 2. 
      Overall, 27 (20%) and 26 (20%) volunteers had >/=1 AE at least possibly related to 
      darunavir and cobicistat, respectively. CONCLUSIONS: Bioequivalence of the 
      darunavir/cobicistat 800/150-mg FDC was demonstrated versus darunavir and 
      cobicistat co-administered as single agents under fasted or fed conditions. Food 
      increased darunavir exposure, therefore, darunavir/cobicistat should be 
      administered with food.
FAU - Kakuda, Thomas N
AU  - Kakuda TN
AD  - Janssen Research & Development, LLC, Titusville, NJ, USA. tkakuda@its.jnj.com.
FAU - Van De Casteele, Tom
AU  - Van De Casteele T
FAU - Petrovic, Romana
AU  - Petrovic R
FAU - Neujens, Mark
AU  - Neujens M
FAU - Salih, Hiba
AU  - Salih H
FAU - Opsomer, Magda
AU  - Opsomer M
FAU - Hoetelmans, Richard Mw
AU  - Hoetelmans RM
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140625
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Carbamates)
RN  - 0 (Drug Combinations)
RN  - 0 (Sulfonamides)
RN  - 0 (Thiazoles)
RN  - LW2E03M5PG (Cobicistat)
RN  - YO603Y8113 (Darunavir)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Carbamates/administration & dosage/adverse effects/pharmacokinetics/*pharmacology
MH  - Cobicistat
MH  - Darunavir
MH  - *Drug Combinations
MH  - Drug Monitoring
MH  - Female
MH  - *Food/adverse effects
MH  - *Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Sulfonamides/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
MH  - Therapeutic Equivalency
MH  - Thiazoles/administration & dosage/adverse effects/pharmacokinetics/*pharmacology
MH  - Young Adult
EDAT- 2014/06/26 06:00
MHDA- 2015/08/06 06:00
CRDT- 2014/06/26 06:00
PHST- 2014/05/06 00:00 [accepted]
PHST- 2014/06/26 06:00 [entrez]
PHST- 2014/06/26 06:00 [pubmed]
PHST- 2015/08/06 06:00 [medline]
AID - 10.3851/IMP2814 [doi]
PST - ppublish
SO  - Antivir Ther. 2014;19(6):597-606. doi: 10.3851/IMP2814. Epub 2014 Jun 25.