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We want to look at the effect of several drugs on the metabolism of
in microsomes and hepatocytes. However, out resources are limited so we
want to incubate at a single concentration rather than look at multiple
I would appreciate any advice on how to assess the effect on metabolism.
Is it best to look at loss of parent as a percentage? If so, then what
should I compare it to? Should I incubate with boiled
hepatocytes/microsomes? Or add the parent drug at the end of the
Or should I prepare a standard curve of parent drug and metabolites and
quantify what remains/is formed for each incubation? If so, then what
matrix should I use to prepare this?
This is the first time I have done such studies so any advice would be
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I myself have not conducted drug interaction studies, however i have
done drug metabolism studies in tissue homogenates and S9 fractions. i
understand when you say that ur resourcesa are very limited implies to
the drug and not to the tissue. i would like to perform is an
incubation having the control with no drug (blank
microsomes/hepatocytes), microsomes/hepatocytes with substrate drug
only, microsomes/hepatocytes with interacting drug only, and
microsomes/hepatocytes containing both substrate and interacting drug.
if possible try analyse the protein content and the protein binding of
both drugs in all scenarios. sampling time would depend how fast or
slow ur drug is being metabolized. its normally recommended that the
reaction rates are calculated in the initial phase of the incubation
where its normally linear.
but quantitaive information on the Km and Vmax would have been more
useful if you had different concentrations running simultaneously (which
u cannot as mentioned).
Do you plan to evaluate the kinetics invitro or its more on a
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