Aaps J
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Physiologically based pharmacokinetic (PBPK) models can over-predict maximum plasma concentrations (C(max)) following intravenous administration. A proposed explanation is that invariably PBPK models report the concentration in the central venous compartment, rather than the site where the samples are drawn. The purpose of this study was to identify and validate potential corrective models based on anatomy and physiology governing the blood supply at the site of sampling and incorporate them into a PBPK platform. ⋯ The model was particularly relevant for studies where traditional PBPK models over-predict early time point concentrations. A successful corrective model for C(max) prediction has been developed, subject to further validation. These models can be enrolled as built-up modules into PBPK platforms and potentially account for factors that may affect the initial mixing of the blood at the site of sampling.