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Dear David
So many side issues have been thrown up in recent correspondence on cmax/AUC
that I thought I would take Walt Woltosz's points separately (with new
subject headings?)
Intuitively, one might consider that absorption means the amount of drug
disappearing from the absorption site and crossing the membrane. However, in
classical pharmacokinetic analysis the researcher is trying to interpret
plasma concentration-time curves and this almost always comes down to fitting
an equation such as the Bateman function to the data (to find Ka and Ke); the
resulting Ka therefore refers to the appearance of drug in the systemic
circulation. Hence not only loss of drug by gut wall metabolism but
extensive first-pass metabolism by the liver will result in reduced
absorption by this definition against all intuitive expectations of what we
mean by absorption. This is a confusion that has existed in my personal
experience for at least thirty years. I recall a German definition that
referred to 'invasion' rather than absorption that goes some way to resolving
the confusion.
Joe Chamberlain
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)