Parallel absorption model (two lag times)

From:"Atul" Subject:[NMusers] Parallel absorption model (two lag times) Date:Sun, February 3, 2002 11:12 am Hello All I am trying to model a two absorption periods (first order) from the same dose. I checked the nmusers archive and it was lot informative. I am not sure if the control stream below has any fundamental mistakes. I checked simulations first and they were fine. When I was trying to do the estimation step the model was repeatedly failed to converge. I included few lines from the data set in which I gave the same dose to two compartments (two parallel sites of absorption). I assumed B1 as the bioavailability factor from 1st compartment and B2(=1-B1) from the second. I was not sure how NONMEM will detect two lag times to model double peaks. Do I need to include andy IF statements? Could somebody please correct me in the code and the way I arranged the dataset. Thanks a lot in advance for your time. Venkatesh Atul Bhattaram Post-doctoral Fellow University of Florida $INPUT ID TIME DV AMT CMT EVID MDV $DATA DATA.CSV IGNORE=C $SUBROUTINES ADVAN6 TRAN 1 TOL=3 $MODEL COMP=(1); DOSE, 1 COMP=(2); DOSE, 2 COMP=(3); CENTRAL, 2 COMP=(4); PERIPHERAL $PK TVCL=THETA(1) TVV=THETA(2) TVK12=THETA(3) TVK21=THETA(4) TALAG1=THETA(5) TALAG2=THETA(6) TVKA=THETA(7); ABSORPTION RATE CONSTANT 1 TVB1=THETA(8); B1 IS BIOAVAILABILITY FACTOR TVKB=THETA(9); ABSORPTION RATE CONSTANT 2 CL=TVCL*EXP(ETA(1)) V=TVV*EXP(ETA(2)) K12=TVK12*EXP(ETA(3)) K21=TVK21*EXP(ETA(4)) ALAG1=TALAG1*EXP(ETA(5)) ALAG2=TALAG2*EXP(ETA(6)) KA=TVKA*EXP(ETA(7)) B1=TVB1*EXP(ETA(8)) KB=TVKB*EXP(ETA(9)) B2=1-B1 S3=V/1000 K10=CL/V $DES DADT(1)= -B1*KA*A(1) DADT(2)=-B2*KB*A(2) DADT(3)=B1*KA*A(1)+B2*KA*A(2)-K12*A(3)+K21*A(4)-K10*A(3) DADT(4)=K12*A(3)-K21*A(4) C=A(3)/S3 $ERROR Y=F*(1+ERR(1))+ERR(2) IPRED=F IRES=DV-IPRED $THETA (0.00001, 70); CL (0.00001, 10); V (0.00001, 1.05); K12 (0.00001, 0.5); K21 (0.00001, 0.001); ALAG1 (0.08, 1.5, 12); ALAG2 (0.00001, 4.5); KA (0.00001, 0.2, 1); B1 (0.00001, 2); KB $OMEGA (0.2); CL (0.2); V (0.2); K12 (0.2); K21 (0.2); ALAG1 (0.2); ALAG2 (0.2); KA (0.2); F (0.1) $SIGMA (0.1) (10) ;$SIMULATION(9215690) ONLYSIM SUBPROBLEMS=100 $EST METHOD=1 NSIG=3 MAXEVAL=9999 PRINT=5 NOABORT POSTHOC ;$COV $TABLE ID TIME CL V K12 K21 ALAG1 ALAG2 KA B1 B2 KB CMT DV IPRED NOPRINT ONEHEADER FILE=TXX CID TIME DV AMT CMT EVID MDV 1 0 0 378 1 1 1 1 0 0 378 2 1 1 1 0.083 96.82 0 3 0 0 1 0.167 2179.48 0 3 0 0 1 0.25 4797.74 0 3 0 0