Back to the Top
Dear readers,
In the PK study of a compound in rats, it was found that by increasing
the
oral dose 2 folds or 3 folds, the AUC was quite more than proportionally
increased and total clearance was slightly decreased at higher doses.
It was,
however,found that the half-life too was decreased at higher doses and
more
noticably the volume of distribution had decreased considerably at higher
doses.
Can this situation be explained by the possible saturation of tissue
binding
at higher doses and also a saturation of clearance (leading to somewhat
decreased cL vlaues at higher doses)but to a lesser extent?!!
It had been noted that the fraction of glucuronides in the urine
(collected
over 24 hrs)had been reduced at higher doses, presumably due to cofactor
depletion.
It was also interstingly noted that after iv-bolus dosing over the same
dose
range the kinetics were overall linear.
If saturable tissue binding is indeed a possibility, why is it happening
only
in the oral case?!
<binding and possible integration into DNA of cells, as it is a nucleoside
mimic>>
Can anyone offer any advice about this situation?
Thank you
Panteha
Back to the Top
Check the Pharmacpkinetics of the drug under study. Does it obey linear
Pharmacokinetics(zero,first orderetc) or non linear pharmacokinetics eg
Michealis menten equation. Give the appropiate
explanation
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)