After a single intravenous (IV) dose of Dolutegravir, plasma clearance is low in rats (0.23 mL/min/kg) and monkeys (2.12 mL/min/kg). The half-lives in rats and monkeys are similar, approximately 6 hours, and the steady-state volume of distribution (VSS) is low. Upon oral administration, Dolutegravir is rapidly absorbed with high oral bioavailability when administered as a solution to fasted male rats and a single monkey (75.6% and 87.0%, respectively). Dolutegravir exposure (Cmax and AUC) increases with dose escalation 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^[3].

The EC50 values of Dolutegravir (S/GSK1349572) against HIV-1 are 0.51 nM in PBMCs, 0.71 nM in MT-4 cells, and 2.2 nM in the PHIV assay, utilizing 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 μM, respectively. In unstimulated and stimulated PBMCs, the CC50 values are 189 μM and 52 μM, respectively. Based on the PBMCs' EC50 value for Dolutegravir against HIV-1 (i.e., 0.51 nM), the cell-based therapeutic index is at least 9,400^[1].