RE: PD lag time in $DES

From: "mathangi" mathangi@msn.com Subject: RE: [NMusers] PD lag time in $DES Date: Thu, November 18, 2004 10:02 am Dr.Jiang, If I understand your question correctly, I am assuming you want to model the delay in your pharmacodynamic response using an indirect response model. If it is so, below is an example and part of the code for an iv bolus - one compartment model and inhibitory indirect response model . $SUBROUTINE ADVAN6 TRANS1 TOL=3 $MODEL COMP = CENTRAL COMP = EFFECT $PK CL = CLI ; INDIVIDUAL CLEARANCE IN L/HR V = VI ; INDIVIDUAL VOLUME OF DISTRIBUTION IN L KIN = THETA(1)*EXP(ETA(1)) ; BASAL ZERO ORDER PRODUCTION RATE OF BIOMARKER KOUT = THETA(2)*EXP(ETA(2)) ; BASAL FIRST ORDER RATE CONSTANT FOR ELIMINATION ; OF BIOMARKER IC50 = THETA(3)*EXP(ETA(3)) ;CONCENTRATION OF DRUG AT 50% OF MAXIMUM OF INHIBITION S1 = V S2 = 1 F2 = KIN/KOUT ;BASELINE RESPONSE; R0 = KIN/KOUT $DES DADT(1) = -CL/V*A(1) ;PLASMA COMPARTMENT INH = A(1)/(IC50+A(1)) ;INHIBITORY FUNCTION DADT(2) = KIN*(1-INH)-KOUT*A(2) ; INDIRECT RESPONSE MODEL I And accordingly, the data file can be arranged by including AMT=1 for CMT=2 at TIME=0 to initialise the response compartment. Please let me know, if this is what you wanted. Thanks Mathangi