Bioequivalence and Bioavailability Forum

Dear Shireen

please note that a pre-dose level (prior first dosing) may indicate an intrinsic level of the substance to be investigated. The assay to asses the concentration in the plasma may not be able to distinguish between the endogenous substance and the administered substance. In this case, not adjusting for an intrinsic level may lead to a biased assessment of the terminal half-life/terminal elimination rate. In fact, terminal half-life increases as your last sampling time point increases.

hope this helps

Martin

PS.: A very simple adjustment (from a personal point of view) is to subtract the pre-infusion value from all contractions assessment post study drug administration. If a concentration level at a specific time point post study drug administration is lower or equal than the corresponding pre-infusion level, this concentration level and all subsequent concentration levels should not be used for calculation of at least terminal half-life / terminal elimination rate.