Re: Time varying volume of distribution implementation

Thorsten, Time varying V is no different from time varying CL (or any other parameter). You should use the variable T in $DES, not TIME, in order to have the time at the instant the DEQ solver evaluates $DES. T may occur anywhere in the interval between the previous record TIME and the current record TIME. TIME in $PK, $DES and $ERROR is the time at the end of the $DES solution interval. The other thing that you may wish to do is to assign the random effect expression for V and CL in $PK so that you can estimate the random variability after accounting for the fixed effect variability in WT. An expression involving ETA() cannot be used in $DES so it has to be assigned in $PK. e.g. $PK POP_V=THETA(1) POP_CL=THETA(2) WT_ZERO=THETA(3) WT_ALPHA=THETA(4) PPV_V=EXP(ETA(1)) ; random effect for V (PPV_V=population parameter variability for V) PPV_CL=EXP(ETA(2)) ; random effect for CLT (PPV_CL=population parameter variability for CL) $DES ;Variable names e.g. DWT_T are used in $DES because the same variable names cannot be assigned in both $DES and in $ERROR DWT_T=WT_ZERO + WT_ALPHA*T ; fixed effect prediction of WT at T ; Biology requires V and CL must both be functions of WT DGRP_V=POP_V*DWT_T/70 DV=DGRP_V*PPV_V ; "individual" V at T using random effect for V DGRP_CL=POP_CL*(DWT_T/70)**(3/4) DCL=DGRP_CL*PPV_CL ; "individual" CL at T using random effect for CL DADT(1)= -DCL*A(1)/DV $ERROR WT_T=WT_ZERO + WT_ALPHA*TIME ; fixed effect prediction of WT at the TIME of the current record GRP_V=POP_V*WT_T/70 GRP_CL=POP_CL*(WT_T/70)**(3/4) V=VT*PPV_V ; "individual" V at the TIME of the current record CL=GRP_CL*PPV_CL ; "individual" CL at the TIME of the current record C=A(1)/V You may, of course, add random effects to WT_ZERO and/or WT_ALPHA as well as having random effects on V and CL. BTW You should consider using the term postmenstrual age rather than gestational age. Gestational age is a single value defined at the time of delivery according to the American Academy of Pediatrics (Engle et al 2004). Postmenstrual age is a continuous variable which may be used during pregnancy and after birth to represent the biological age of the fetus/child. Best wishes, Nick Engle WA. Age terminology during the perinatal period. Pediatrics. 2004;114(5):1362-4.