Yilmaz Aylin, Izadkhashti Arash, Price Richard W, Mallon Patrick W, De Meulder Marc, Timmerman Philip, Gisslén Magnus
Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
AIDS Res Hum Retroviruses. 2009 Apr;25(4):457-61. doi: 10.1089/aid.2008.0216.
Darunavir is the most recently licensed protease inhibitor currently used in treatment-experienced HIV-infected individuals. Our objective was to determine darunavir concentrations in cerebrospinal fluid (CSF) and plasma in subjects receiving antiretroviral treatment regimens containing ritonavir-boosted darunavir. Darunavir concentrations were determined by liquid chromatography tandem mass spectrometry in 14 paired CSF and plasma samples from eight HIV-1-infected individuals. The lower limit of quantification was 5.0 ng/ml. All of the 14 CSF samples had detectable darunavir concentrations with a median darunavir concentration of 34.2 ng/ml (range 15.9-212.0 ng/ml). The median (range) plasma darunavir concentration was 3930 (1800-12900) ng/ml. All CSF samples had detectable darunavir concentrations. Most of them exceeded or were in the same range as levels needed to inhibit replication of wild type virus, making it probable that darunavir, at least to some extent, contributes to the suppression of HIV replication in the central nervous system.
地瑞那韦是目前用于接受过治疗的HIV感染者的最新获批的蛋白酶抑制剂。我们的目的是确定接受含利托那韦增强的地瑞那韦抗逆转录病毒治疗方案的受试者脑脊液（CSF）和血浆中的地瑞那韦浓度。通过液相色谱串联质谱法测定了来自8名HIV-1感染者的14对脑脊液和血浆样本中的地瑞那韦浓度。定量下限为5.0 ng/ml。14份脑脊液样本中均检测到地瑞那韦浓度，地瑞那韦浓度中位数为34.2 ng/ml（范围15.9 - 212.0 ng/ml）。血浆地瑞那韦浓度中位数（范围）为3930（1800 - 12900）ng/ml。所有脑脊液样本均检测到地瑞那韦浓度。其中大多数超过或处于抑制野生型病毒复制所需水平的相同范围内，这使得地瑞那韦至少在一定程度上有助于抑制中枢神经系统中的HIV复制成为可能。
