Bioequivalence and Bioavailability Forum

dear atish !

note that there is a difference between dose-proportionality and dose-linearity. the existence of dose-proportionality implies also dose-linearity but not vice versa.

when you would like to show dose-proportionality you have to ensure that a dose of zero leads to an AUC of zero (you have no intrinsic level of the substance investigated = baseline value of zero) this is identical to an intercept of zero when you plot AUC (y-scale) versus dose on the (x-scale). A simple regression analysis may be misleading when you have an saturable absorption or saturable metabolism at high doses investigated. for this reason, I suggest to check simply your baseline levels.

the following paper gives a nice introduction on this topic: Hummel at al (2008). Exploratory assessment of dose proportionality: review of current approaches and proposal for a practical criterion. Pharmaceutical statistics, early view.

a more complicated topic is the statistical identification (with a given type I error) of a dose range where dose-proportionality holds. this problem can be formulated as a sequence of hypothesis testing problems similar as in dose-finding studies as on the assumption of dose-proportionaliy AUC/dose = µ (i.e. constant for all doses investigated).

hope this helps

martin