SEARCH

SEARCH BY CITATION

Disclaimer: Supplementary materials have been peer-reviewed but not copyedited.

FilenameFormatSizeDescription
bdrb21053-sup-0001-supmat.doc294K

Fig. S1. Plasma concentrations of MR16-1 after a single intravenous administration of MR16-1 to female mice at a dose of 5mg/kg (▪) or 50 mg/kg (□). Data represent individual values of five animals at each dose. After administration of 5 mg/kg, the plasma MR16-1 concentration decreased over time, and became lower than the quantification limit (0.977 μg/ml) seven days after administration in all five animals. Moreover, the rate of MR16-1 elimination from plasma tended to increase from three days after administration in all individuals. After administration of 50 mg/kg, the plasma MR16-1 concentration decreased over time, and became lower than the quantification limit 11 days after administration in the individual showing the fastest elimination, and 25 days after administration in that showing the slowest elimination. The rate of MR16-1 elimination from plasma also tended to increase from days 7 to 14 onwards in four of the five animals.

Fig. S2. Plasma concentration of MR16-1 in males (A) and females (B) in the preliminary study were simulated based on a model built on previously reported multiple dose male and female fertility studies (CLlin: 0.239 and 0.432 ml/hr/kg, respectively) as well as on data from a single-dose pharmacokinetic study (CLlin: 0.926 ml/hr/kg). The approach taken is equivalent to the one used to model the human pharmacokinetic data for Actemra (Frey et al., 2010) and for many monoclonal antibodies in general (Dirks and Meibohm, 2010). This includes two pharmacokinetic compartments and parallel linear and saturable (nonlinear) clearance pathways. Simulations for the 15 mg/kg MR16-1 preceded by a single loading dose of 50 mg/kg are shown as lines, and each symbol represents the observed value of individual animals. Samples were collected from different animals at each time point (n=3).

Table S1. IC50 values of MR16-1 for inhibition of mouse IL-6–induced 7TD1 cell growth

Table S2. Pharmacokinetic parameters after a single intravenous administration of MR16-1 to female mice at a dose of 5 or 50mg/kg

Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.