Using MIXture model to fit 1 compartment vs 2 compartment model

I have a small data set of 4 samples each from 15 patients getting CVVH for renal failure that was handed to me. Some subjects appear to be modeled best by a 1 compartment model, other by a 2 compartment model. I have tried the ctl stream below using MIX to allow NONMEM to fit to either a 1 or 2 cmpt model, and it appears to work well (Note there is high covariance in CL, V1, and Q,V2, so their respective ETAs are shared). However, I have two questions to the group: 1. Is this the optimal way to allow NONMEM to fit to a 1 vs 2 compt model? 2. Is this appropriate? That is, the drug likely is best modeled by (at least) a 2 compartment model, yet only a fraction (~20%) of these sparse data sets appear best fit by a 2 compt model. Given that the sampling was not optimized to detect/characterize a 2 compartment model, should I settle and report a one compartmental model, or describe a 2 cmpt when possible? Perhaps is it an angels on a pinhead issue, as my primary objective is to describe any effect of dialysate flow on clearance. $INPUT ID TIME CLCK=DROP AMT RATE SS II DV LGDV WGT HGT DURD FLOW CMPD EVID $DATA Zosyn.CSV IGNORE=# IGNORE(CMPD=2) $SUBROUTINES ADVAN6 TOL=3 $MODEL NPARAMS=7 NCOMP=2 COMP=(CENTRAL DEFDOSE) COMP=(TISSUE) ; 2 COMPARTMENT MODEL ; CMPD 1 = Piperacillin ; CMPD 2 = Tazobactam $MIX NSPOP=2 P(1)=THETA(7) P(2)=1-THETA(7) P1C = THETA(7) $PK CALLFL=1 EST=MIXEST CL1=THETA(1)*EXP(ETA(1)); TVV1=THETA(2)*EXP(ETA(1)); CL2=THETA(1)*THETA(3)*EXP(ETA(2)) TVV2=THETA(2)*THETA(4)*EXP(ETA(2)) FLG=1 IF (MIXNUM.EQ.2) FLG=0 CL=FLG*CL1 + (1-FLG)*CL2 V1 = FLG*TVV1 + (1-FLG)*TVV2 Q=THETA(5)*(1-FLG) V2 = THETA(6)**(1-FLG); V2 cannot be 0 for 1 compt due to K21=Q/V2 divide by 0 fault S1=V1 K10 = CL*(FLOW/35)/V1 K12 = (Q/V1)*(1-FLG) K21 = (Q/V2)*(1-FLG) $DES DADT(1) = -A(1) * (K10 + K12) + A(2) * K21 DADT(2) = A(1) * K12 - A(2) * K21 -- Paul R. Hutson, Pharm.D. Associate Professor UW School of Pharmacy T: 608.263.2496 F: 608.265.5421