RE: PD lag time in $DES

From: "Nick Holford" n.holford@auckland.ac.nz Subject: RE: [NMusers] PD lag time in $DES Date: Thu, November 25, 2004 4:20 am Mark, mark.e.sale@gsk.com wrote: > > But, there is not, as far as I know, an (easy) way to store what the value was at (T-LAG) using $DES. > The value of a response at T-LAG can be obtained by creating a model with a duplicate set of compartments. One set of compartments is used to predict the response at T and the other at T-LAG. You need to replicate the dosing history for each set of compartments. e.g. for the simple case of a one compartment disposition with first order absorption: ID TIME AMT CMT DV 1 0 100 1 . 1 0 100 3 . ... $MODEL COMP (GUT) COMP (CP) COMP (GUTLAG) COMP (CPLAG) $PK ALAG3=THETA(lag) ... $DES DGUT=A(1) DCP=A(2) ; the value of the non-lagged conc RATEIN=KA*GUT DADT(1)=-RATEIN DADT(2)=RATEIN - DCP*CL DGUTL=A(3) DCPLAG=A(4) ; the value of the lagged conc RATELG=KA*GUTL DADT(3)=-RATELG DADT(4)=RATELG - DCPLAG*CL This DE model can be easily extended to describe a turnover model (aka indirect effect) to create a lagged effect. This code gives you simultaneous access to both the current conc/effect and the lagged conc/effect in $DES. The only tricky part of this model is the need to keep track of any time varying covariates that you might be using so that you use the correct time associated value of the covariate to influence the current or lagged compartment parameters. Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/ _______________________________________________________