[1-[2′,5′-Bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-methyl-thymine]-3′-spiro-5″-(4″-amino-1″,2″-oxathiole-2″ (TSAO-m3T) is a potent, selective and specific inhibitor of human immunodeficiency virus type 1 replication in vitro. Uptake of TSAO-m3T by human CEM cells is drug concentration-dependent and increased proportionally with increasing initial extracellular TSAO-m3T concentrations up to 20 μg/mL. Within 6 hr of incubation, the cells were almost completely saturated with the test compound; further incubation up to 72 hr did not markedly increase the intracellular concentration of the compound. No intracellular metabolic conversion of TSAO-m3T was observed in CEM, MT-4 or MOLT-4 cells. Upon intravenous bolus administration of TSAO-m3T to mice at 0.75 mg/kg, TSAO-m3T was rapidly cleared from the plasma in a mono-exponential manner (half-life: 22 min; distribution volume: 9.5 L/kg; total body clearance: 17.8 L/hr/kg). TSAO-m3T mainly accumulated in the lungs, followed by the heart, kidney and liver. Significant amounts of different metabolites of TSAO-m3T were detected in most tissues, the liver, kidney and spleen being the organs that showed the most extensive metabolism. The principal metabolites identified were TSAO-m3T derivatives in which the t-butyldimethylsilyl moiety at C-2′ and/or C-5′ had been split off. The free base N3-methylthymine was not detected.

中文翻译：

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抗HIV-1特异性抑制剂[1- [2'，5'-Bis-O-（叔丁基二甲基甲硅烷基）-β-d-呋喃呋喃糖基] -3-N-甲基胸腺嘧啶] -3的代谢和药代动力学′-spiro-5″-（4″-氨基-1″，2″-草硫醇-

TSAO-m3T以单指数方式从血浆中快速清除（半衰期：22分钟；分配体积：9.5 L / kg；总体清除率：17.8 L / hr / kg）。TSAO-m3T主要积累在肺中，其次是心脏，肾脏和肝脏。在大多数组织中检测到大量不同的TSAO-m3T代谢产物，肝脏，肾脏和脾脏是表现出最广泛代谢的器官。确定的主要代谢产物是TSAO-m3T衍生物，其中C-2'和/或C-5'处的叔丁基二甲基甲硅烷基部分已被分离出来。未检测到游离碱N3-甲基胸腺嘧啶。在大多数组织中检测到大量不同的TSAO-m3T代谢产物，肝脏，肾脏和脾脏是表现出最广泛代谢的器官。确定的主要代谢产物是TSAO-m3T衍生物，其中C-2'和/或C-5'处的叔丁基二甲基甲硅烷基部分已被分离出来。未检测到游离碱N3-甲基胸腺嘧啶。在大多数组织中检测到大量不同的TSAO-m3T代谢产物，肝脏，肾脏和脾脏是表现出最广泛代谢的器官。确定的主要代谢产物是TSAO-m3T衍生物，其中C-2'和/或C-5'处的叔丁基二甲基甲硅烷基部分已被分离出来。未检测到游离碱N3-甲基胸腺嘧啶。