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Dear readers,
We have been studying PK of a compound, which seems to exhibit dose-dependency
in its PK behaviour at higher doses. The F estimates that were obtained(based
on a linear kinetics assumption) and were calculated from the dose-corrected
comparisons of iv and oral data, were in the range of 0.68 to 1, depending on
the dose that was studied. The cumulative amount of the drug excreted
unchanged in the urine (24 h collection)as fraction of the dose, however, was
very small (~2-3%)in general. So, if we were to calculate F based on urinary
data, we would have very little bioavailability!
Can anyone offer any explanation for this discrepancy?
Is it possible that urinary excretion of this compound, had been already
saturated at doses lower than our lowest studied dose?
Any suggestions would be appreciated.
Back to the Top
Dear readers,
We have been studying PK of a compound, which seems to exhibit dose-dependency
in its PK behaviour at higher doses. The F estimates that were obtained(based
on a linear kinetics assumption) and were calculated from the dose-corrected
comparisons of iv and oral data, were in the range of 0.68 to 1, depending on
the dose that was studied. The cumulative amount of the drug excreted
unchanged in the urine (24 h collection)as fraction of the dose, however, was
very small (~2-3%)in general. So, if we were to calculate F based on urinary
data, we would have very little bioavailability!
Can anyone offer any explanation for this discrepancy?
Is it possible that urinary excretion of this compound, had been already
saturated at doses lower than our lowest studied dose?
Any suggestions would be appreciated.
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Hello,
Have you considered the metabolism of this drug? There may not be
any 'unchanged
drug' left by the time it is in the elimination phase.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)