modelling flow-dependent clearance

From rs@chdr.leidenuniv.nl Mon Dec 11 16:40:20 1995 Subject: modelling flow-dependent clearance To anyone who can give me a clue... I'm trying to model the kinetics of a test-drug with high hepatic clearance given as an intravenous infusion (single compartment kinetics to start with). Clearance of the drug is assumed dependent on hepatic blood flow which is measured using echo-doppler techniques, and which can vary continously over time. It seems to me that I need to model the kinetics using a differential equation (e.g. using ADVAN6) in which clearance is some function (presumably linear) of measured flow. So far so good. The trouble is that I'm pretty certain that I need flow-estimates in between the actual measurements in order to adequately define the process. Something as simple as linear interpolation or else some smooth function would suffice but I have no clue as to the implementation of such a function in NONMEM. Naturally, if someone could convince me that this is not necessary, I'd be more than pleased... Grateful for any response, Rik Schoemaker CHDR, Leiden, The Netherlands

From R.Port@dkfz-heidelberg.de Tue Dec 12 00:55:16 1995 Subject: interpolation with diff. eqn. Re.: Interpolated "driver" of differential equation, Rik Schoemaker's message of Tue, Dec 12; Lewis' message of Mon, Dec 11 Hi Lewis, do you think one could use (T - TIME) for time elapsed since last record, e.g. > $PROBLEM An Example of interpolated "driver" of Diff Eqn > $INPUT ID TIME DV INT SLOP ; SLOP = increment per time elapsed since last record > $DATA data > $SUBROUTINES ADVAN6 TOL=5 > > $MODEL > COMP=CENTRAL > > $PK > B=INT > M=SLOP > CL = THETA(1)*EXP(ETA(1)) $DES TT = T - TIME X = B + M*TT DADT(1) = -X*CL ?? Ruedi ------------------------------------------------------------------------------- R.E. Port, Dept. 0420, German Cancer Research Center P.O. Box 10 19 49, D-69009 Heidelberg phone: x49-6221 42-3385 -3347 fax: -3346 e-mail: r.port@dkfz-heidelberg.de