Back to the Top
Dear All,
You will be highly appreciated if you could
provide me your opinions and information about
how to analyze the relationship between
administered doses and pharmacological effects
by certain types of expressions. I don't know whether
those equations for concentration-effect relationship
apply to the dose-effect relationship and under what
conditions if they apply. I am also interested in
the interspecies scaling for PD parameters or
parameters from above dose-effect analysis. Will
the power exponent of 0.7 applys too?
Tony Lee
Email: p2149z.-a-.hotmail.com
Back to the Top
"Tony Lee (by way of David Bourne )" wrote:
> how to analyze the relationship between
> administered doses and pharmacological effects
> by certain types of expressions. I don't know whether
> those equations for concentration-effect relationship
> apply to the dose-effect relationship and under what
> conditions if they apply.
There is really no difference between dose and conc-effect models. You just
have to assume that conc has a constant value proportional to the dose (or
dose rate). If dose rate is constant then you can assume conc is dose
rate/clearance and model the effects as a function of average steady state
conc. You dont have to know the clearance. You can assume a nominal value of 1.
C=DoseRate/Clearance
If you want to describe a delay in onset of drug effect then the effect
compartment model is easily applied:
Ce(t) = DoseRate/Clearance*(1-exp(-Keq*t))
where Keq=ln(2)/Teq and Teq is the equilibration half-time.
> I am also interested in
> the interspecies scaling for PD parameters or
> parameters from above dose-effect analysis. Will
> the power exponent of 0.7 applys too?
PD parameters that describe functional properties of body e.g. cardiac
output, can be expected to scale with an allometric exponent of 3/4 (the
theory predicts this fraction; you can of course use 0.75 but not 0.7!)
PD parameters reflecting concentration sensitivity (e.g. EC50) are not
expected to scale with body size.
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, Private Bag 92019, Auckland, New Zealand
email:n.holford.-at-.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556
http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm
Back to the Top
One small addition to Nick's note: Whereas we do not expect parameters
like IC50's
to scale with body size, we oftentimes see that they scale with interspecies
differences in drug receptor binding (...of course accounting for
differences in
free drug concentrations).Some other PD effects which are mediated via
turnover (e.g., indirect response
models) can also be scaled between species when the constitutive turnover
kinetics
of the substrate being measured is known.
Regards, Jeff
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)