$PROB Karmakar Data $DATA alldata.txt $INPUT ID AGE WT HT GRP AV TIME C LGC=DV MDV ;Notes: ; Group 1 has epinephrine, Group 2 has no epinephrine ; AV = 1 = arterial ; AV = 2 = venous $SUBROUTINE ADVAN6 TOL=3 $MODEL COMP(CENTRAL) COMP(PERIPH) COMP(VENOUS) $PK CALLFL=1 ;estimated parameters IF (GRP.EQ.1) THEN BIO1=THETA(1)*EXP(ETA(1)) ; Bioavailability 1 ELSE BIO1=THETA(2)*EXP(ETA(1)) ; Bioavailability 1 ENDIF MAT1=THETA(3)*EXP(ETA(2)) ; Mean Absorption Time 1 CV1 =THETA(4)*EXP(ETA(3)) ; CV 1 BIO2=THETA(5)*EXP(ETA(4)) ; Bioavailability 2 MAT2=THETA(6)*EXP(ETA(5)) ; MAT2 CV2 =THETA(7)*EXP(ETA(6)) ; CV2 KAV =THETA(8)*EXP(ETA(7)) ; KAV ; Known parameters DOSE = 2 * WT ; Dose in paper was 2 mg/kg ;IV Kinetic function ;From Excel Spreadsheet, based on Anesthesiology 87:1308, 1997 V1 = 24/80*WT K21=0.011 K10=0.014 K12=0.0055 $DES ;Compute absorption rate at TIME F11= MAT1/(6.28*TIME*TIME*TIME*CV1*CV1) F21= F11**0.5 F31= (MAT1-TIME)*(MAT1-TIME)/(2*CV1*CV1*MAT1*TIME) I1 = BIO1*DOSE*F21*EXP(-F31) F12= MAT2/(6.28*TIME*TIME*TIME*CV2*CV2) F22= F12**0.5 F32= (MAT2-TIME)*(MAT2-TIME)/(2*CV2*CV2*MAT2*TIME) I2 = BIO2*DOSE*F22*EXP(-F32) ;3 compartment differential equations DADT(1)=K21*A(2)-A(1)*(K10+K12)+I1+I2 DADT(2)=K12*A(1)-K21*A(2) DADT(3)=KAV*(A(1)-A(3)) ; Note - no effort to do mass balance $ERROR IF (AV.EQ.1) THEN TY=A(1)/V1 ELSE TY=A(3)/V1 ENDIF IF (MDV.EQ.1) THEN TY = 1 ENDIF ;" WRITE(*,*) TIME, DOSE, KA, TY IF(TY.GT.0) THEN LTY = LOG(TY) ELSE EXIT 1 ENDIF Y=LTY + EPS(1) $THETA .55 FIX ; Bioavailability 1 w epi .71 FIX ; Bioavailability 1 w/o epi 18.3 FIX ; Mean Absorption Time 1 5.53 FIX ; CV 1 .825 FIX ; Bio2 715 FIX ; Mean Absorption Time 2 1.14 FIX ; CV 2 0.446 FIX ; AV Equilibration delay $OMEGA .1 .1 .1 .1 .1 .1 .1 $SIGMA .039 $ESTIMATION SIG=3 MAX=2000 PRINT=1 NOABORT METHOD=0 POSTHOC $TABLE ID DOSE GRP AV KAV BIO1 MAT1 CV1 BIO2 MAT2 CV2 TIME LTY