Table IV.
Dosing Scenarios and Effects on mAb and L In Vivo Equilibrium
Conditions | Equilibrium favors mAb–L to | Resulting analytes | Comment | |
---|---|---|---|---|
Associate | Dissociate | |||
High mAb/L; high affinity | X | mAbfree, mAbbound, and Lbound | Assumes independent and equivalent binding of L to each of the bivalent binding sites on mAb | |
mAb/L ∼1; or low affinity | X | Mixed forms | Dosing may increase L to mAb/L ∼1 (16) | |
High L; slow clearance of L, or increase L production | X | mAbbound, Lbound, and Lfree | L can accumulate if the off rate from mAb is slower than the degradation, resulting in longer T1/2 (17) | |
Disease status/matrix | Case dependent | Individual matrix variability requires tests on samples from multiple patient donors (18) |
mAb monoclonal antibody drugs, L target ligand