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I have a compound that is active in the 5-10 microM range. The
compound will ultimately be dosed orally, but I want to confirm
activity in an animal model. What is the best way to select a drug
dose for ip administration to target 5-10 microM plasma levels?
Steve
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The following message was posted to: PharmPK
Hi Steve
You can use the following equation to calculate the dose needed to
acheive 5-10 microM conc.
Dose=(CssAve*CL*Tau)/F
Where Css Ave is the average conc during the dosing interval, CL is
the predicted clearance based on preclinical drug metabolism studies
or CL obtained in other animal models (after allometric
normalization), Tau: dosing interval say every 12 hours and F will
the estimated bioavailability by IP route which will be dependent on
lipophilicity of your molecule but usually 0.3-0.5. Now as you can
see many of these factors are estimated so the calculated dose will
be somewhat inaccuarate but you can always do a pilot study in a few
animals, collect and analyze blood samples after repeated dosing and
see how far the observed conc is from the desired conc range and then
adjust the dose to reach the desired conc range.
Hope it helps
Fatemeh
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