Re: Parallel absorption model (two lag times)

From:Nick Holford Subject:Re: [NMusers] Parallel absorption model (two lag times) Date:Mon, February 4, 2002 1:15 am There is a problem in DADT(1) and DADT(2). You apply the bioavailability fractions B1 and B2 to loss from these compartments but the loss from these dose compartments is not affected by bioavailability. It is the input to compartments 3 and 4 only that need these bioavailability fractions. Note that you can make use of the PREDPP basic PK parameters F1 and F2 to do the job for you instead of using B1 and B2. There is also a typo in DADT(3). I think you mean to have KB (not KA) multiply A(2). The line C=A(3)/S3 is unnecessary and will only slow down execution. > $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 > I would also suggest you consider parameterizing the model in terms of CL, V1, Q and V2. I cannot think of any good reason to use the K12 and K21 parameterization. I would use something like the following: $SUBROUTINES ADVAN6 TOL=3 ; TRANS 1 is the default $MODEL COMP=(1); DOSE, 1 COMP=(2); DOSE, 2 COMP=(3); CENTRAL, 2 COMP=(4); PERIPHERAL $PK KA=THETA(KA) KB=THETA(KB) ALAG1=THETA(ALAG1) ALAG2=THETA(ALAG2) CL=THETA(CL) V1=THETA(V1) Q=THETA(Q) V2=THETA(V2) F1=THETA(F1) F2=1-F1 S3=V1/1000 $DES ;define variables to reduce computation and make code clearer RINA=KA*A(1) RINB=KB*A(2) C3=A(3)/V1 C4=A(4)/V2 DADT(1)=-RINA DADT(2)=-RINB DADT(3)=RINA + RINB + C4*Q - C3*(Q + CL) DADT(4)=Q*(C3-C4) $ERROR C=F ;=A(3)/S3 Y=C*(1+ERR(1)) + ERR(2) Note also that because your model is linear you could use ADVAN5 provided you stick to the naming conventions for parameters and do the necessary algebra in $PK to convert CL, V1, Q and V2 into the appropriate rate constants and V variables. This should run faster than ADVAN6. Nick -- Nick Holford, Divn Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/