Back to the Top
Dear readers,
Is it possible for a drug to show saturable tissue binding (greatly lowered
Vd)at higher (single) ORAL doses only, but not at higher (single) IV-BOLUS
doses?
Can anyone suggest a possible mechanism leading to such an effect?
Thanks
Panteha
Back to the Top
Dear Panteha,
One possible explanation to your observations is the presence
of a metabolite that competes with the parent drug for the same tissue binding
sites.
After oral administration and due to first pass effect, plasma metabolite
concentrations might be high enough to displace the parent drug from its
binding,
resulting in a decrease in the apparent volume of distribution.
You can try to model your observations and estimate the tissue affinity
constants for
drug and metabolite in a similar way it is possible to model the
pharmacodynamic
interaction between a drug and metabolite without having the metabolite plasma
concentrations.
Best regards,
Iñaki.
Iñaki F. Trocóniz Ph. D
Farmacia y Tecnología Farmacéutica
Facultad de Farmacia
Universidad de Navarra
Pamplona 31080
Spain
e-mail: itroconiz.-at-.unav.es
Back to the Top
If you are getting lowered Vd/F after higher oral doses, maybe you have
saturable first-pass metabolism (increased F at higher doses).
Hope this helps,
Varun
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)