arterio-venous modeling

From: rs@chdr.leidenuniv.nl Subject: arterio-venous modeling Date: 26 Sep 1997 08:48:10 -0400 Dear fellow users, I'm trying to model concentration effect relationships for propofol and midazolam and I run into proteresis. I have a more or less linearly increasing concentration using a target controlled infusion (TCI) regime (with a duration of somewhere between 30 and 90 min) followed by a 30 min plateau phase after which the infusion terminates. The TCI means that I cannot do ordinary PK modeling because of the continuously varying input rate and I hoped to be able to model using ordinary linear interpolation, specifying slope and intercept of the interpolating segments. This works very well for an ordinary effect compartment situation with hysteresis. However, I have venous concentrations and (especially for propofol) proteresis which I assume is due to arterio-venous differences. The problem is (I assume) that for hysteresis the measured concentrations drive the hypothetical effect compartment concentrations that are related to the effect while in this case the arterial concentrations that drive the venous concentrations are related to the effect. Do you agree about the assumption of arterio-venous differences and does anyone have suggestions for modeling this specific situation? Thanks in advance, Rik Schoemaker CHDR, Leiden, The Netherlands