# PharmPK Discussion - Applied Dose-Effect Relation?

PharmPK Discussion List Archive Index page
• On 23 Jun 2000 at 20:33:16, "Tony Lee" (p2149z.-at-.hotmail.com) sent the message
`Dear All,You will be highly appreciated if you couldprovide me your opinions and information abouthow to analyze the relationship betweenadministered doses and pharmacological effectsby certain types of expressions. I don't know whetherthose equations for concentration-effect relationshipapply to the dose-effect relationship and under whatconditions if they apply. I am also interested inthe interspecies scaling for PD parameters orparameters from above dose-effect analysis. Willthe power exponent of 0.7 applys too?Tony LeeEmail: p2149z.-a-.hotmail.com`
Back to the Top

• On 25 Jun 2000 at 20:57:45, Nick Holford (n.holford.-at-.auckland.ac.nz) sent the message
`"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 justhave to assume that conc has a constant value proportional to the dose (ordose rate). If dose rate is constant then you can assume conc is doserate/clearance and model the effects as a function of average steady stateconc. You dont have to know the clearance. You can assume a nominal value of 1.C=DoseRate/ClearanceIf you want to describe a delay in onset of drug effect then the effectcompartment 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. cardiacoutput, can be expected to scale with an allometric exponent of 3/4 (thetheory predicts this fraction; you can of course use 0.75 but not 0.7!)PD parameters reflecting concentration sensitivity (e.g. EC50) are notexpected to scale with body size.--Nick Holford, Dept Pharmacology & Clinical PharmacologyUniversity of Auckland, Private Bag 92019, Auckland, New Zealandemail:n.holford.-at-.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm`
Back to the Top

• On 29 Jun 2000 at 18:26:17, Jeff Wald (jwald.-at-.pharsight.com) sent the message
`One small addition to Nick's note:  Whereas we do not expect parameterslike IC50'sto scale with body size, we oftentimes see that they scale with interspeciesdifferences in drug receptor binding (...of course accounting fordifferences infree drug concentrations).Some other PD effects which are mediated viaturnover (e.g., indirect responsemodels) can also be scaled between species when the constitutive turnoverkineticsof the substrate being measured is known.Regards, Jeff`
Back to the Top

Want to post a follow-up message on this topic? If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Applied Dose-Effect Relation?" as the subject

Copyright 1995-2010 David W. A. Bourne (david@boomer.org)