TK Evaluation

LNA-i-miR-221 quantification was performed using the rat plasma by LC-MS/MS analysis, as previously described.19^,20 The TK evaluation was performed using non-compartmental analysis on Phoenix WinNonlin software, version 6.4 (Pharsight, Mountain View, CA, USA) at CiToxLAB. TK parameters were determined from the mean concentration of the matrix samples collected from different animals at each time point (sparse sampling model). A separate TK analysis was performed for each sex and sampling occasion. The standard deviation (SD) and CV were calculated to assess inter-individual variability. The absence of quantifiable levels of LNA-i-miR-221 at pre-dose (before the first administration) and in control animals was evaluated (see also Supplemental Materials and Methods).