Department of Neurosciences, University of California, San Diego, San Diego, California, USA.
Antimicrob Agents Chemother. 2012 Apr;56(4):1985-9. doi: 10.1128/AAC.05098-11. Epub 2012 Jan 30.
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.
在脑脊液（CSF）中达到更高浓度的抗逆转录病毒药物与更好地控制 HIV 在 CSF 中的复制以及可能更好的神经认知功能有关。本研究的目的是确定 CSF 中安普那韦（APV）的浓度是否在治疗范围内。根据包含福沙那韦（FPV）的方案选择个体，FPV 是 APV 的前药，并且可以获得储存的 CSF 和匹配的血浆。通过高效液相色谱法（HPLC）（血浆）或液相色谱串联质谱法（LC/MS/MS）（CSF）测量了 75 名患者的 119 对 CSF-血浆配对样本中的总 APV。将浓度与野生型 HIV 的 50%抑制浓度（IC₅₀）（5.6ng/ml）进行比较。受试者主要为中年（中位数 44 岁）白人（57%）男性（78%），患有 AIDS（77%）。除了 4 个 CSF 标本外，所有标本均检测到 APV，中位数浓度为 24.8ng/ml（四分位距 [IQR]，16.2 至 44.0）。CSF 与血浆的中位数比值为 0.012（IQR，0.008 至 0.018）。CSF 浓度与血浆浓度相关（rho=0.61；P<0.0001），与给药后采样间隔相关（rho=-0.29；P=0.0019）。在检测到 APV 的 CSF 标本中，超过 97%的 CSF 标本中的 CSF 浓度超过野生型 HIV 的中位数 IC₅₀，中位数为 4.4 倍（IQR，2.9 至 7.9）。我们得出结论，福沙那韦的给药应有助于作为有效抗逆转录病毒方案的一部分控制中枢神经系统（CNS）中的 HIV 复制。
