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Does anyone know how to dose an antibody based on half-life? For
example, if half-life is 5-7 days, should it be dosed every week? I
am worried about potential accumulation resulting in increased
immunogenicity.
KC
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KC,
The immunogenic response may depend on all sorts of things, some
kinetically influenced some not, and may have a complex relationship
with the dose of your agent. But in terms of the kinetics per se the
half-life has nothing to do with "accumulation" of the MAb to steady-
state (if that is what you want) which is determined only by the dose
and the clearance.
The half-life value determines how long it takes to approach steady-
state (about 5 half lives) on repeated dosing, and the fluctuation
between the peak and trough values of your MAb in blood - Dosing
intervals much shorter than half-life mean little fluctuations, dosing
intervals much longer then the half-life mean large fluctuations, but
the average steady-state concentration in both cases will be
unaffected, provided the maintenance dose per unit time (and of course
clearance) stays unchanged. As a convenient compromise between these 2
extremes, many drugs are dosed at intervals close to the half-life, so
if the antibody half-life is 5-7 days then a dosing interval of a week
is probably optimal.
Cheers
BC
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