Therapeutic Amprenavir Concentrations in Cerebrospinal Fluid

被引：13

作者：

Croteau, David ^{[1
]}

Letendre, Scott ^{[2
]}

Best, Brookie M. ^{[3
,5
]}

Rossi, Steven S. ^{[3
]}

Ellis, Ronald J. ^{[1
]}

Clifford, David B. ^{[6
]}

Collier, Ann C. ^{[7
]}

Gelman, Benjamin B. ^{[8
]}

Marra, Christina M. ^{[7
]}

McArthur, Justin ^{[9
]}

McCutchan, J. Allen ^{[2
]}

Morgello, Susan ^{[10
]}

Simpson, David M. ^{[10
]}

Way, Lauren ^{[4
]}

Capparelli, Edmund ^{[3
]}

Grant, Igor ^{[4
]}

机构：

[1] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA

[2] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA

[3] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA

[4] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA

[5] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA

[6] Washington Univ, St Louis, MO USA

[7] Univ Washington, Seattle, WA 98195 USA

[8] Univ Texas Med Branch, Galveston, TX USA

[9] Johns Hopkins Univ, Baltimore, MD USA

[10] Mt Sinai Sch Med, New York, NY USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2012年 / 56卷 / 04期

基金：

美国国家卫生研究院;

关键词：

IMMUNODEFICIENCY-VIRUS-INFECTION; ANTIRETROVIRAL THERAPY; HIV RNA; COGNITIVE DISORDERS; CNS; COMBINATION; LOPINAVIR; DEMENTIA; TYPE-1; BRAIN;

D O I：

10.1128/AAC.05098-11

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 (IC50) 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 IC50 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.

引用

页码：1985 / 1989

页数：5

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