Absolute brain accumulation of MLs in Mdr1ab(−/−) and wild-type mice as a function of the administrated dose.

<p>IVM (filled squares) or MOX (empty squares) was administered to Mdr1ab(−/−) mice or to wild-type mice at increasing doses. Highest doses used for each ML were below the LD₅₀ to ensure a non-lethal effect of the administration. Mice in each group were sacrificed 24 h after treatment and drug concentrations were determined in brain and plasma. Absolute brain accumulation was plotted against the administrated dose in (<b>A</b>) Mdr1ab(−/−) or (<b>B</b>) wild-type mice. A positive and significant linear correlation was observed between brain uptake and the administered dose rate (R²>0.94 in all cases). All measurements are expressed as mean ± S.D. of six animals.