R.C. Schoemaker, J. Burggraaf & A.F. Cohen
CHDR, Leiden, The Netherlands
Hepatic blood flow is a major determinant in the rate of elimination of so-called high clearance drugs. Knowledge about this flow may be obtained by continuous IV infusion of a test compound with a high hepatic clearance. We illustrate how the resulting concentration profile of such a test compound may be translated into clearance and flow profiles. For certain specific flow patterns an explicit expression may be obtained for the concentration profile. Indocyanine green (ICG) plasma concentration profiles during exercise can be modelled by assuming a succession of situations with constant clearance. Knowledge of certain aspects of the kinetics of the test- compound may be all that is needed to translate the concentration-profile into a flow-profile; a point to point translation into clearance per time point for the same ICG data is possible if the volume of distribution is known. Knowledge of an additional predictor-profile may be merged with the concentration-profile to obtain a complete picture of blood flow through the liver. Two-compartment sorbitol kinetics can be described using a system of differential equations where portal vein flow measured with echo-Doppler is used as a predictor for total hepatic flow and sorbitol clearance. This set of equations can be solved simultaneously for all subjects using NONMEM.
Reference: PAGE 5 () Abstr 554 [www.page-meeting.org/?abstract=554]
Poster: poster