PMID- 33368327
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20211220
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 61
IP  - 7
DP  - 2021 Jul
TI  - Effect of Renal and Hepatic Impairment on the Pharmacokinetics of Temsavir, the 
      Active Moiety of Fostemsavir.
PG  - 939-953
LID - 10.1002/jcph.1810 [doi]
AB  - The oral prodrug fostemsavir (GSK3684394, formerly BMS-663068) is an 
      antiretroviral treatment for HIV-1. Fostemsavir is metabolized to its active 
      moiety, temsavir, a first-in-class HIV-1 attachment inhibitor that binds to the 
      viral envelope glycoprotein 120. Long-term antiretroviral therapy, the resulting 
      longer life expectancy, and/or certain coinfections can increase the risk of 
      chronic liver and kidney disease in HIV-1-infected individuals. Two studies were 
      conducted to collectively evaluate the impact of renal and hepatic impairment on 
      temsavir pharmacokinetics (PK) and safety following a single dose of a 600-mg 
      extended-release fostemsavir tablet. There was no clinically meaningful effect of 
      renal or hepatic impairment on temsavir PK, although renal clearance decreased 
      with increasing renal impairment from moderate to severe, and exposure (maximum 
      concentration and area under the plasma concentration-time curve from time 0 to 
      infinity) tended to increase with increasing severity of hepatic impairment. No 
      clinically meaningful effect of hemodialysis on temsavir PK parameters was 
      observed. Fostemsavir was generally safe and well tolerated by treated subjects. 
      Most adverse events (AEs) were mild, with the exception of 1 patient in the renal 
      impairment study who discontinued due to 2 serious AEs unrelated to the study 
      drug. No other treatment-emergent serious AEs occurred, and no other AEs leading 
      to discontinuation were reported. Overall, these results suggest that fostemsavir 
      can be used without dose modification in subjects with mild to severe renal 
      impairment, including those with end-stage renal disease on hemodialysis, and in 
      subjects with mild to severe hepatic impairment.
CI  - (c) 2020, The American College of Clinical Pharmacology.
FAU - Magee, Mindy
AU  - Magee M
AD  - GlaxoSmithKline, Upper Providence, Pennsylvania, USA.
FAU - Slater, Jill
AU  - Slater J
AD  - ViiV Healthcare, Research Triangle Park, North Carolina, USA.
FAU - Mannino, Frank
AU  - Mannino F
AD  - GlaxoSmithKline, Upper Providence, Pennsylvania, USA.
FAU - Ackerman, Peter
AU  - Ackerman P
AD  - ViiV Healthcare, Branford, Connecticut, USA.
FAU - Llamoso, Cyril
AU  - Llamoso C
AD  - ViiV Healthcare, Branford, Connecticut, USA.
FAU - Moore, Katy
AU  - Moore K
AD  - ViiV Healthcare, Research Triangle Park, North Carolina, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210118
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Organophosphates)
RN  - 0 (Piperazines)
RN  - 0 (Prodrugs)
RN  - 97IQ273H4L (fostemsavir)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Anti-HIV Agents/*pharmacokinetics/therapeutic use
MH  - Body Mass Index
MH  - Creatinine/blood
MH  - Female
MH  - Glomerular Filtration Rate
MH  - HIV Infections/drug therapy
MH  - Hepatic Insufficiency/*epidemiology/metabolism
MH  - Humans
MH  - Liver Function Tests
MH  - Male
MH  - Middle Aged
MH  - Organophosphates/*pharmacokinetics/therapeutic use
MH  - Patient Acuity
MH  - Piperazines/*pharmacokinetics/therapeutic use
MH  - Prodrugs
MH  - Racial Groups
MH  - Renal Insufficiency/*epidemiology/metabolism
MH  - Sex Factors
OTO - NOTNLM
OT  - HIV-1
OT  - fostemsavir
OT  - hepatic impairment
OT  - pharmacokinetics
OT  - renal impairment
OT  - temsavir
EDAT- 2020/12/29 06:00
MHDA- 2021/12/21 06:00
CRDT- 2020/12/28 12:26
PHST- 2020/11/06 00:00 [received]
PHST- 2020/12/23 00:00 [accepted]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
PHST- 2020/12/28 12:26 [entrez]
AID - 10.1002/jcph.1810 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2021 Jul;61(7):939-953. doi: 10.1002/jcph.1810. Epub 2021 Jan 
      18.