Table 3. IVM and MOX concentrations in brain and brain-to-plasma ratio at increasing dose rates in Mdr1ab(−/−) and wild-type mice.

MLs	Mdr1ab(−/−)	Wild-type
Ivermectin
LD50 (µmol/kg)	0.46a	27–34b
Brain concentration at LD50  (pmol/g)	270c	170–215d
Brain-to-plasma ratio (ml/g)	5.5 (R2 = 0.973)e	0.08 (R2 = 0.990)e
Moxidectin
LD50 (µmol/kg)	2.3a	70–131b
Brain concentration at LD50  (pmol/g)	830c	740–1380d
Brain-to-plasma ratio (ml/g)	2.6 (R2 = 0.936)e	0.09 (R2 = 0.984)e

IVM or MOX was administered to Mdr1ab(−/−) mice (6 per dose rate) or to wild-type mice (3 per dose rate) at increasing doses below the LD₅₀ to ensure a non-lethal effect of the administration. Drug concentrations were determined in brain and plasma after animals were sacrificed at 24 h post-treatment. Absolute brain accumulation was plotted against the plasma concentration to determine brain concentration at LD₅₀, brain-to-plasma concentration ratio calculated and R².

^aLD₅₀ determined graphically from Figure 1.

^bLD₅₀ for IVM and MOX determined from the literature [20], [21].

^cBrain concentration reached at LD₅₀, determined graphically from Figure 3A.

^dBrain concentration reached at LD₅₀, determined graphically from Figure 3B.

^eBrain-to-plasma concentration ratio calculated and R² obtained from the slope of the linear relationship between brain concentration and plasma concentration, which quantifies blood-brain transport.