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All,
Does anyone out there know the plasma protein binding of Olanzapine in
rats and guinea pigs? I have only found values for human plasma
(around 90%). I have seen in some studies that much higher total
plasma levels is needed to obtain pharmacological activity in rats and
guinea pigs compared to reported efficacious therapeutic levels in
humans and was just wondering if this could (partly) be attributed to
higher protein binding in rats and guinea pigs (i.e. lower free
fraction) .
Thanks,
Chris
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Hi Chris
Summerfield et al 2008 Xenobiotica 38 1518 give rat and human (but not
Guinea pig)
fuB (B=blood) as essentially the same (0.135 and 0.134). If you assume
the BP ratio
to be insignificantly different then fup (p=plasma) are also expected to
be
insignificantly different ... but I don't have exp BP values. Of course
there will
be interindividual variability (IIV) of fup related to the IIV of
binding protein
concentrations ... and you have to define what you mean by
(in)significant too ...
but that's another topic ...
regards
David
David Turner, PhD
Principal Scientist - Modelling and Simulation
Simcyp Limited
Blades Enterprise Centre, John Street, Sheffield, S2 4SU, UK
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