PMID- 25870057
OWN - NLM
STAT- MEDLINE
DCOM- 20160407
LR  - 20240324
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 59
IP  - 7
DP  - 2015 Jul
TI  - Pharmacokinetic interactions between BMS-626529, the active moiety of the HIV-1 
      attachment inhibitor prodrug BMS-663068, and ritonavir or ritonavir-boosted 
      atazanavir in healthy subjects.
PG  - 3816-22
LID - 10.1128/AAC.04914-14 [doi]
AB  - BMS-663068 is a prodrug of BMS-626529, a first-in-class attachment inhibitor that 
      binds directly to HIV-1 gp120, preventing initial viral attachment and entry into 
      host CD4(+) T cells. This open-label, multiple-dose, four-sequence, crossover 
      study addressed potential two-way drug-drug interactions following 
      coadministration of BMS-663068 (BMS-626529 is a CYP3A4 substrate), atazanavir 
      (ATV), and ritonavir (RTV) (ATV and RTV are CYP3A4 inhibitors). Thirty-six 
      healthy subjects were randomized 1:1:1:1 to receive one of four treatment 
      sequences with three consecutive treatments: BMS-663068 at 600 mg twice daily 
      (BID), BMS-663068 at 600 mg BID plus RTV at 100 mg once daily (QD), ATV at 300 mg 
      QD plus RTV at 100 mg QD (RTV-boosted ATV [ATV/r]), or BMS-663068 at 600 mg BID 
      plus ATV at 300 mg QD plus RTV at 100 mg QD. Compared with the results obtained 
      by administration of BMS-663068 alone, coadministration of BMS-663068 with ATV/r 
      increased the BMS-626529 maximum concentration in plasma (Cmax) and the area 
      under the concentration-time curve in one dosing interval (AUCtau) by 68% and 
      54%, respectively. Similarly, coadministration of BMS-663068 with RTV increased 
      the BMS-626529 Cmax and AUCtau by 53% and 45%, respectively. Compared with the 
      results obtained by administration of ATV/r alone, ATV and RTV systemic exposures 
      remained similar following coadministration of BMS-663068 with ATV/r. BMS-663068 
      was generally well tolerated, and there were no adverse events (AEs) leading to 
      discontinuation, serious AEs, or deaths. Moderate increases in BMS-626529 
      systemic exposure were observed following coadministration of BMS-663068 with 
      ATV/r or RTV. However, the addition of ATV to BMS-663068 plus RTV did not further 
      increase BMS-626529 systemic exposure. ATV and RTV exposures remained similar 
      following coadministration of BMS-663068 with either ATV/r or RTV. BMS-663068 was 
      generally well tolerated alone or in combination with either RTV or ATV/r.
CI  - Copyright (c) 2015, American Society for Microbiology. All Rights Reserved.
FAU - Zhu, Li
AU  - Zhu L
AD  - Bristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA 
      li.zhu@bms.com.
FAU - Hruska, Matthew
AU  - Hruska M
AD  - Bristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
FAU - Hwang, Carey
AU  - Hwang C
AD  - Bristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
FAU - Shah, Vaishali
AU  - Shah V
AD  - Bristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
FAU - Furlong, Michael
AU  - Furlong M
AD  - Bristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
FAU - Hanna, George J
AU  - Hanna GJ
AD  - Bristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
FAU - Bertz, Richard
AU  - Bertz R
AD  - Bristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
FAU - Landry, Ishani Savant
AU  - Landry IS
AD  - Bristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150413
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-HIV Agents)
RN  - 0 (BMS-626529)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (HIV Fusion Inhibitors)
RN  - 0 (Organophosphates)
RN  - 0 (Piperazines)
RN  - 0 (Triazoles)
RN  - 0 (gp120 protein, Human immunodeficiency virus 1)
RN  - 4MT4VIE29P (Atazanavir Sulfate)
RN  - 97IQ273H4L (fostemsavir)
RN  - O3J8G9O825 (Ritonavir)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anti-HIV Agents/adverse effects/*pharmacokinetics/therapeutic use
MH  - Atazanavir Sulfate/adverse effects/pharmacokinetics/*therapeutic use
MH  - Cross-Over Studies
MH  - Drug Interactions
MH  - Drug Therapy, Combination
MH  - Female
MH  - HIV Envelope Protein gp120/metabolism
MH  - HIV Fusion Inhibitors/adverse effects/pharmacokinetics/*therapeutic use
MH  - HIV-1/drug effects
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Organophosphates/therapeutic use
MH  - Piperazines/adverse effects/pharmacokinetics/*therapeutic use
MH  - Ritonavir/adverse effects/pharmacokinetics/*therapeutic use
MH  - Triazoles/adverse effects/pharmacokinetics/*therapeutic use
MH  - Young Adult
PMC - PMC4468697
EDAT- 2015/04/15 06:00
MHDA- 2016/04/08 06:00
PMCR- 2016/01/01
CRDT- 2015/04/15 06:00
PHST- 2014/12/24 00:00 [received]
PHST- 2015/04/05 00:00 [accepted]
PHST- 2015/04/15 06:00 [entrez]
PHST- 2015/04/15 06:00 [pubmed]
PHST- 2016/04/08 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - AAC.04914-14 [pii]
AID - 04914-14 [pii]
AID - 10.1128/AAC.04914-14 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2015 Jul;59(7):3816-22. doi: 10.1128/AAC.04914-14. 
      Epub 2015 Apr 13.