Dolutegravir (sodium)

1051375-19-9

C20H18F2N3NaO5

DMSO : >= 4.5 mg/mL (10.20 mM); H2O : < 0.1 mg/mL (insoluble)

Metabolic Enzyme/Protease; Anti-infection

Dolutegravir sodium is an inhibitor of HIV-1 integrase-catalyzed strand transfer with IC₅₀ of 2.7 nM. IC50 & Target: IC50: 2.7 nM (HIV-1 integrase)^[1] In Vitro: The EC₅₀ of Dolutegravir (S/GSK1349572) against HIV-1 is 0.51 nM in PBMCs, 0.71 nM in MT-4 cells, and 2.2 nM in the PHIV assay, which uses a pseudotyped self-inactivating virus. The 50% cytotoxic concentrations (CC₅₀) for Dolutegravir in proliferating IM-9, U-937, MT-4, and Molt-4 cells are 4.8, 7.0, 14, and 15 uM, respectively. In unstimulated and stimulated PBMCs, the CC₅₀ are 189 uM and 52 uM, respectively. Based on the EC₅₀ of Dolutegravir against HIV-1 in PBMCs (i.e., 0.51 nM), this translates to a cell-based therapeutic index of at least 9, 400^[1]. In Vivo: Following a single intravenous (IV) administration of Dolutegravir, the plasma clearance is low in rats (0.23?mL/min/kg) and monkeys (2.12?mL/min/kg). The half-lives in the rat and monkey are similar, approximately 6?h, and the steady-state volume of distribution (V_SS) is low. Following oral administration, Dolutegravir is rapidly absorbed with a high oral bioavailability when administered as a solution to fasted male rats and a single monkey (75.6 and 87.0%, respectively). Dolutegravir exposure (C_max and AUC) increased with increasing dose following oral administration of a suspension to non-fasted rats up to 250?mg/kg and non-fasted monkeys up to 50?mg/kg, although the increase is less than proportional^[2].