Table 2.

Pharmacokinetics/pharmacodynamics after a single intravenous or oral dose of GBT1118 to mice

Dose, mg/kg	n	Route	Tmax, h	Blood Cmax, µM	ΔP50, %	%Hb Occupancy
10	24	iv	0.17	408 ± 70	17 ± 2	19 ± 3
70	9	po	4–6	682 ± 68	54 ± 4	32 ± 3
100	18	po	4–6	836 ± 93	64 ± 4	39 ± 4
140	9	po	4–6	1,134 ± 190	77 ± 6	54 ± 9

Values are means ± SD; n, number of mice. Blood samples were also analyzed for effects on Hb O₂ affinity using O₂ equilibrium curves. Percent occupancy was calculated by dividing GBT1118 blood concentration obtained at C_max by Hb concentration (~2.15 mM) in blood, as defined by percent hematocrit (43% hematocrit). An increase in GBT1118 concentration in blood was accompanied by an increase in Hb O₂ affinity, as evidenced by increase in ∆P₅₀.