Abstract
Toxicokinetic data have traditionally been presented as maximum observed plasma concentrations ( C max) and area under the concentration time curve (AUC) values. These values have been used to compare exposures across studies and species to provide valuable interpretation of drug safety data. Increasingly, questions are asked of toxicology studies to more accurately describe the concentration effect relationships in terms of compound affinity for target and off-target receptors. C max values can immediately be referenced to known pharmacological activities, particularly when the extent of plasma protein binding is taken into account. This provides a measure of the more pharmacologically relevant free drug exposure. AUC values on the other hand contain the component of time, which means that direct comparison to pharmacological activity values are not immediately possible. Conversion of AUC to average plasma concentration ( C av) provides a simple and convenient means to allow such a comparison without losing any information imparted by AUC values. In this paper, the benefit and advantage of applying C av values is illustrated using examples taken from the literature.
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