Re: arterio-venous modeling

From: Mark Sale <msale@medlib.iaims.georgetown.edu> Subject: Re: arterio-venous modeling Date: 26 Sep 1997 09:55:26 -0400 Rik, You're correct that in the explicit ADVANS it isn't easy to do a continuosly chaning infusion rate. However, it can be done in the differential equation advans, by making an infusion rate a function of time, and checking to see if all drug has been infused. This could then explain the arterial compartment, and the effect compartment and venous compartment could be attached to that with (linear?) rate constants. At the end of this is a control stream and data file. But I'd geuss other may have more clever ways of doing this. As far as you suggestion that proteresis can result from A-V difference, where the effect compartment is the arterial compartment and the sample is collected from the venous compartment, you're correct, in a rapidly changing system (i.e., rate constants on the order of 2/min) this can occur, even in the absence of tissue extraction. The other common explaination is tolerance. I'd refer you to the "classic" paper descriibing tolerance to nicotine by Porchet and Sheiner. Mark Mark Sale M.D. Assistant Professor of Medicine Georgetown University Washington DC 20007 202-687-8242 msale@medlib.georgetown.edu $PROB infusions $INPUT TIME AMT DV $SUBROUTINES ADVAN6 TOL = 5 $DATA DATA $MODEL COMP = (DEPOT,DEFDOSE) COMP = (CENTRAL,DEFOBS) $PK RATE = 1 ;THIS DEFINES THE RATE, COULD ALSO BE INCLUDED IN DATA SET S2 = THETA(1) KEL = THETA(2) $DES ;FIRST CHECK TO SEE IF ANY DRUG LEFT IN COMPARTMENT ;THE TOTAL DOSE INFUSED IS LISTED IN THE DATA SET ;THIS IS THEN INFUSED, AT A VARYING RATE UNTIL IT ;IS GONE IF(A(1).LE.0) THEN IND = 0 ELSE IND =1 END IF DADT(1) = -RATE*IND*T ;INFUSION RATE IS FUNCTION OF TIME DADT(2) = RATE*IND*T-KEL*A(2) $ERROR Y = F+ERR(1) $THETA (0,1) ;VOLUME (0,1) ;KEL $OMEGA 1 $ESTIMATION MAX=9999 PRINT=2 $TABLE TIME IND NOPRINT FILE = OUT.XLS ....................... data 0 50 . 0.5 . 3 1 . 7 1.5 . 10 2 . 12 2.5 . 17 3 . 20 3.5 . 22 4 . 25 5 . 30 6 . 35 7 . 40 8 . 45 9 . 50 10 . 55 11 . 48 12 . 44 13 . 40