PMID- 29930812
OWN - NLM
STAT- MEDLINE
DCOM- 20181231
LR  - 20240318
IS  - 2052-1707 (Electronic)
IS  - 2052-1707 (Linking)
VI  - 6
IP  - 4
DP  - 2018 Jul
TI  - The safety, tolerability, and pharmacokinetic profile of GSK2838232, a novel 2nd 
      generation HIV maturation inhibitor, as assessed in healthy subjects.
PG  - e00408
LID - 10.1002/prp2.408 [doi]
LID - e00408
AB  - This work aimed to assess the safety, tolerability, pharmacokinetics (PK), and 
      relative bioavailability of GSK2838232, an investigational HIV maturation 
      inhibitor. GSK2838232 was administered over four dose-escalation studies in 
      healthy subjects which assessed single oral doses (5-250 mg) and repeat doses (up 
      to 200 mg once or twice daily) +/-100 mg ritonavir (RTV) once daily. GSK2838232 
      administration (up to 250 mg) to 124 subjects across four studies resulted in few 
      mild adverse events (AEs) with similar frequencies to placebo. There were no 
      clearly identified drug-related AEs. GSK2838232 tested fasted was quickly 
      absorbed with a t(max) of 2-3 hours. With food, the absorption was delayed and 
      more variable, with ~60% increase in AUC and C(max). Overall, following single 
      doses GSK2838232 AUC and C(max) generally exhibited proportional PK from 50 to 
      100 mg dose without RTV and from 50 to 250 mg with RTV and following repeated 
      doses of 20-200 mg with RTV. In relative bioavailability studies, a micronized 
      formulation was found to be suitable for development. At steady state, RTV 
      increased GSK2838232 AUC and C(max) by 10- and 3-fold, respectively. Half-life 
      was prolonged from ~17 hours nonboosted to ~34 hours with RTV. This boosting 
      effect was also seen in repeat-dose GSK2838232 studies, which achieved the 
      targeted plasma exposure with GSK2838232 as a once-daily regimen of up to 200 mg 
      with RTV. The results of these studies demonstrated a favorable safety and PK 
      profile for GSK2838232 and support its investigation for the treatment of HIV 
      infection.
FAU - Johnson, Mark
AU  - Johnson M
AUID- ORCID: 0000-0002-0747-9697
AD  - GlaxoSmithKline Research Triangle Park NC USA.
FAU - Jewell, Roxanne C
AU  - Jewell RC
AD  - GlaxoSmithKline Research Triangle Park NC USA.
FAU - Peppercorn, Amanda
AU  - Peppercorn A
AD  - GlaxoSmithKline Cambridge MA USA.
FAU - Gould, Elizabeth
AU  - Gould E
AD  - GlaxoSmithKline Research Triangle Park NC USA.
FAU - Xu, Jianfeng
AU  - Xu J
AD  - GlaxoSmithKline Collegeville PA USA.
FAU - Lou, Yu
AU  - Lou Y
AD  - GlaxoSmithKline Research Triangle Park NC USA.
AD  - Parexel Research Triangle Park NC USA.
FAU - Davies, Matthew
AU  - Davies M
AD  - GlaxoSmithKline Stockley Park NC USA.
FAU - Baldwin, Sandra
AU  - Baldwin S
AD  - GlaxoSmithKline Ware UK.
FAU - Tenorio, Allan R
AU  - Tenorio AR
AD  - GlaxoSmithKline Research Triangle Park NC USA.
FAU - Burke, Matthew
AU  - Burke M
AD  - GlaxoSmithKline King of Prussia PA USA.
FAU - Jeffrey, Jerry
AU  - Jeffrey J
AD  - GlaxoSmithKline Research Triangle Park NC USA.
FAU - Johns, Brian A
AU  - Johns BA
AD  - GlaxoSmithKline Research Triangle Park NC USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180605
PL  - United States
TA  - Pharmacol Res Perspect
JT  - Pharmacology research & perspectives
JID - 101626369
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Butyrates)
RN  - 0 (Chrysenes)
RN  - 0 (Pentacyclic Triterpenes)
RN  - G9C7884M8M (GSK-2838232)
RN  - O3J8G9O825 (Ritonavir)
SB  - IM
MH  - Adult
MH  - Anti-HIV Agents/adverse effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Biological Availability
MH  - Butyrates/adverse effects/*pharmacokinetics
MH  - Chrysenes/adverse effects/*pharmacokinetics
MH  - Double-Blind Method
MH  - Drug Interactions
MH  - Female
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pentacyclic Triterpenes
MH  - Ritonavir/pharmacology
MH  - Young Adult
PMC - PMC5989765
OTO - NOTNLM
OT  - GSK2838232
OT  - HIV maturation inhibitor
OT  - healthy Subjects
OT  - pharmacokinetics
OT  - safety
EDAT- 2018/06/23 06:00
MHDA- 2019/01/01 06:00
PMCR- 2018/06/05
CRDT- 2018/06/23 06:00
PHST- 2018/02/15 00:00 [received]
PHST- 2018/05/15 00:00 [accepted]
PHST- 2018/06/23 06:00 [entrez]
PHST- 2018/06/23 06:00 [pubmed]
PHST- 2019/01/01 06:00 [medline]
PHST- 2018/06/05 00:00 [pmc-release]
AID - PRP2408 [pii]
AID - 10.1002/prp2.408 [doi]
PST - epublish
SO  - Pharmacol Res Perspect. 2018 Jun 5;6(4):e00408. doi: 10.1002/prp2.408. 
      eCollection 2018 Jul.