PMID- 17668559
OWN - NLM
STAT- MEDLINE
DCOM- 20080303
LR  - 20201209
IS  - 1359-6535 (Print)
IS  - 1359-6535 (Linking)
VI  - 12
IP  - 4
DP  - 2007
TI  - Pharmacokinetic interaction between TMC114/r and efavirenz in healthy volunteers.
PG  - 509-14
AB  - BACKGROUND: This open-label, crossover study investigated the pharmacokinetic 
      interaction between TMC114 (darunavir [Prezista]), administered with low-dose 
      ritonavir (TMC114/r) and efavirenz (EFV) in HIV-negative, healthy volunteers. 
      METHODS: Volunteers received TMC114/r 300/100 mg twice daily for 6 days, and once 
      daily on day 7 (session 1). After a 7-day washout period volunteers received EFV 
      600 mg once daily for 18 days (session 2), with coadministration of TMC114/r 
      300/100 mg twice daily from day 11-day 16 and TMC114/r once daily on day 17. 
      RESULTS: When coadministered with TMC114/r, plasma concentrations of EFV were 
      slightly increased. In the presence of TMC114/r, EFV minimum (Cmin) and maximum 
      (Cmax) plasma concentrations increased by 15-17%, and by 21% for EFV area under 
      the curve (AUC24h). TMC114/r and EFV coadministration resulted in TMC114 Cmin, 
      Cmax and AUC12h decreases of 31%, 15% and 13%, respectively. No serious adverse 
      events (AEs) or AEs leading to withdrawal were reported in this trial. Overall, 
      TMC114/r and EFV coadministration was well tolerated. CONCLUSIONS: The clinical 
      significance of the changes in AUC and Cmin seen with TMC114/r and EFV 
      coadministration has not been established; this combination should be used with 
      caution. Similar findings are expected with the approved TMC114/r 600/100 mg 
      twice daily dose.
FAU - Sekar, Vanitha J
AU  - Sekar VJ
AD  - Tibotec, Inc., Yardley, PA, USA. vsekar@tibus.jnj.com
FAU - De Pauw, Martine
AU  - De Pauw M
FAU - Marien, Kris
AU  - Marien K
FAU - Peeters, Monika
AU  - Peeters M
FAU - Lefebvre, Eric
AU  - Lefebvre E
FAU - Hoetelmans, Richard M W
AU  - Hoetelmans RM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Alkynes)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Benzoxazines)
RN  - 0 (Cyclopropanes)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 0 (Sulfonamides)
RN  - JE6H2O27P8 (efavirenz)
RN  - O3J8G9O825 (Ritonavir)
RN  - YO603Y8113 (Darunavir)
SB  - IM
MH  - Adult
MH  - Alkynes
MH  - Anti-HIV Agents/administration & dosage/adverse effects/*pharmacokinetics
MH  - Benzoxazines/administration & dosage/adverse effects/*pharmacokinetics
MH  - Cyclopropanes
MH  - Darunavir
MH  - Drug Interactions
MH  - Drug Therapy, Combination
MH  - HIV Seronegativity
MH  - Humans
MH  - Middle Aged
MH  - Reverse Transcriptase Inhibitors/administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Ritonavir/administration & dosage/adverse effects/*pharmacokinetics
MH  - Sulfonamides/administration & dosage/adverse effects/*pharmacokinetics
MH  - Treatment Outcome
MH  - Volunteers
EDAT- 2007/08/03 09:00
MHDA- 2008/03/04 09:00
CRDT- 2007/08/03 09:00
PHST- 2007/08/03 09:00 [pubmed]
PHST- 2008/03/04 09:00 [medline]
PHST- 2007/08/03 09:00 [entrez]
PST - ppublish
SO  - Antivir Ther. 2007;12(4):509-14.