Limited Sampling with Enterohepatic Recirculation

Good afternoon - I am curious if anyone could tell me if any of the limited sampling design software are able to handle enterohepatic recirculation models. Specifically, I have a model that is coded as follows: $PK IF(AMT.GT.0)PODO=AMT MU_1=LOG(THETA(1)) KA1=EXP(MU_1+ETA(1)) BIO=1 ; bioavailability = 1 for tablet MU_2=LOG(THETA(2)) MTT=EXP(MU_2+ETA(2)) MU_3=LOG(THETA(3)) N=EXP(MU_3+ETA(3)) F1=0 TVK20=THETA(4) K20=TVK20*EXP(ETA(4)) TVV=THETA(5) V=TVV*EXP(ETA(5)) TVK23=THETA(6) K23=TVK23*EXP(ETA(6)) TVK32=THETA(7) K32=TVK32*EXP(ETA(7)) TVK35=THETA(8) K35=TVK35*EXP(ETA(8)) TVK53=THETA(9) K53=TVK53*EXP(ETA(9)) TVK24=THETA(10) K24=TVK24*EXP(ETA(10)) TVK41=THETA(11) K41=TVK41*EXP(ETA(11)) TVMTIME1=THETA(12) MTIME(1)=TVMTIME1*EXP(ETA(12)) TVDUR=THETA(13) MTIME(2)=MTIME(1)+TVDUR*EXP(ETA(13)) S2=V S3=V S6=V K12=KA1 KTR=(N+1)/MTT LNFAC=LOG(2.5066)+(N+0.5)*LOG(N)-N MU_4=LOG(TVK20) MU_5=LOG(TVV) MU_6=LOG(TVK23) MU_7=LOG(TVK32) MU_8=LOG(TVK35) MU_9=LOG(TVK53) MU_10=LOG(TVK24) MU_11=LOG(TVK41) MU_12=LOG(TVMTIME1) MU_13=LOG(TVDUR) $DES DL=1/100000 FLAG=MPAST(1)-MPAST(2) DADT(1)=EXP(LOG(BIO*PODO+DL)+LOG(KTR+DL)+N*LOG(KTR*T+DL)-KTR*T-LNFAC)-K1 2*A(1)+K41*A(4)*FLAG DADT(2)=K12*A(1)-(K23+K20+K24)*A(2)+K32*A(3) DADT(3)=K23*A(2)-(K35+K32)*A(3)+K53*A(5) DADT(4)=K24*A(2)-K41*A(4)*FLAG DADT(5)=K35*A(3)-K53*A(5) Since I am using the MPAST coding in NONMEM to account for the EHR, is there any way that I can use this type of coding (or a variation thereof) with any of the optimal design software programs that are available? If not, I was curious if anyone has any experience with designing limited sampling strategies in the context of enterohepatic recirculation and could possibly give me some advice. Thanks in advance - Al Alexander Berg, Ph.D./Pharm.D. Clinical Pharmacology Fellow Mayo Clinic - Rochester [email protected] 507-284-4303