PMID- 22290964
OWN - NLM
STAT- MEDLINE
DCOM- 20120628
LR  - 20211021
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 56
IP  - 4
DP  - 2012 Apr
TI  - Therapeutic amprenavir concentrations in cerebrospinal fluid.
PG  - 1985-9
LID - 10.1128/AAC.05098-11 [doi]
AB  - Antiretrovirals that reach higher concentrations in cerebrospinal fluid (CSF) are 
      associated with better control of HIV in CSF and possibly better neurocognitive 
      performance. The objective of this study was to determine whether amprenavir 
      (APV) concentrations in CSF are in the therapeutic range. Individuals were 
      selected based on the use of regimens that included fosamprenavir (FPV), a 
      prodrug of APV, and the availability of stored CSF and matched plasma. Total APV 
      was measured in 119 matched CSF-plasma pairs from 75 subjects by high-performance 
      liquid chromatography (HPLC) (plasma) or liquid chromatography tandem mass 
      spectrometry (LC/MS/MS) (CSF). Concentrations were compared to the 50% inhibitory 
      concentration (IC(5)(0)) for wild-type HIV (5.6 ng/ml). Subjects were predominantly 
      middle-aged (median 44 years) white (57%) men (78%) with AIDS (77%). APV was 
      detected in all but 4 CSF specimens, with a median concentration of 24.8 ng/ml 
      (interquartile range [IQR], 16.2 to 44.0). The median CSF-to-plasma ratio was 
      0.012 (IQR, 0.008 to 0.018). CSF concentrations correlated with plasma 
      concentrations (rho = 0.61; P < 0.0001) and with postdose sampling interval (rho 
      = -0.29; P = 0.0019). APV concentrations in CSF exceeded the median IC(5)(0) for 
      wild-type HIV in more than 97% of CSF specimens with detectable APV by a median 
      of 4.4-fold (IQR, 2.9 to 7.9). We conclude that administration of fosamprenavir 
      should contribute to control of HIV replication in the central nervous system 
      (CNS) as a component of effective antiretroviral regimens.
FAU - Croteau, David
AU  - Croteau D
AD  - Department of Neurosciences, University of California, San Diego, San Diego, 
      California, USA. dcroteau@ucsd.edu
FAU - Letendre, Scott
AU  - Letendre S
FAU - Best, Brookie M
AU  - Best BM
FAU - Rossi, Steven S
AU  - Rossi SS
FAU - Ellis, Ronald J
AU  - Ellis RJ
FAU - Clifford, David B
AU  - Clifford DB
FAU - Collier, Ann C
AU  - Collier AC
FAU - Gelman, Benjamin B
AU  - Gelman BB
FAU - Marra, Christina M
AU  - Marra CM
FAU - McArthur, Justin
AU  - McArthur J
FAU - McCutchan, J Allen
AU  - McCutchan JA
FAU - Morgello, Susan
AU  - Morgello S
FAU - Simpson, David M
AU  - Simpson DM
FAU - Way, Lauren
AU  - Way L
FAU - Capparelli, Edmund
AU  - Capparelli E
FAU - Grant, Igor
AU  - Grant I
CN  - CHARTER Group
LA  - eng
GR  - HHSN271201000030C/MH/NIMH NIH HHS/United States
GR  - HHSN271201000027C/MH/NIMH NIH HHS/United States
GR  - U01 MH083545/MH/NIMH NIH HHS/United States
GR  - UL1 RR029887/RR/NCRR NIH HHS/United States
GR  - N01 MH022005/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120130
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Carbamates)
RN  - 0 (Furans)
RN  - 0 (Sulfonamides)
RN  - 5S0W860XNR (amprenavir)
SB  - IM
MH  - Adult
MH  - Anti-HIV Agents/administration & dosage/*cerebrospinal fluid/pharmacokinetics
MH  - Antiretroviral Therapy, Highly Active
MH  - CD4-Positive T-Lymphocytes
MH  - Carbamates/administration & dosage/*cerebrospinal fluid/pharmacokinetics
MH  - Chromatography, High Pressure Liquid
MH  - Drug Administration Schedule
MH  - Drug Therapy, Combination
MH  - Female
MH  - Furans
MH  - HIV Infections/blood/cerebrospinal fluid
MH  - HIV-1
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Male
MH  - Middle Aged
MH  - Sulfonamides/administration & dosage/*cerebrospinal fluid/pharmacokinetics
MH  - Tandem Mass Spectrometry
PMC - PMC3318381
EDAT- 2012/02/01 06:00
MHDA- 2012/06/29 06:00
PMCR- 2012/10/01
CRDT- 2012/02/01 06:00
PHST- 2012/02/01 06:00 [entrez]
PHST- 2012/02/01 06:00 [pubmed]
PHST- 2012/06/29 06:00 [medline]
PHST- 2012/10/01 00:00 [pmc-release]
AID - AAC.05098-11 [pii]
AID - 05098-11 [pii]
AID - 10.1128/AAC.05098-11 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2012 Apr;56(4):1985-9. doi: 10.1128/AAC.05098-11. 
      Epub 2012 Jan 30.