$PROBLEM SIM MODEL

$INPUT ID TIME AMT DV BMI HT CR AGE GEN WT BSA GFR CV1 CV2 CV3 CV4

$DATA DATA.PRN

$SUBROUTINE ADVAN1 TRANS2

$PK

CBMI = (BMI-26.29)/4.093

CHT = (HT-1.586)/0.2

CCR = (CR-0.985)/0117

CAGE = (AGE-38.81)/8.189

CWT = (WT-67.4)/21.2

CBSA = (BSA-1.713)/0.363

CGFR = (GFR-91.4)/37.9

CCV1 = (CV1-101.6)/30.7

CCV2 = (CV2-11)/4.33

CCV3 = (CV3-1.01)/0.209

CCV4 = (CV4-0.098)/0.0198

TVCL = THETA(1)*EXP(THETA(2)*BMI)*EXP(THETA(3)*GFR)

CL = TVCL*EXP(ETA(1))

TVV = THETA(4)*EXP(THETA(5)*BSA)*EXP((1-GEN)*THETA(6))

V = TVV*EXP(ETA(2))

S1 = V

$ERROR

Y = F*EXP(EPS(1)) +EPS(2)

IPRED = F*EXP(EPS(1)) +EPS(2); individual-specific prediction

$THETA (0,0.1); BASELINE CL

$THETA (0,0.04); BMI ON CL

$THETA (0,0.01); crcl oncl

$THETA (0,1); baseline volume

$THETA (0,0.3); bsa on V

$THETA (0,0.3); GEN ON V

$OMEGA BLOCK(2)

.2

0.05 .2

$SIGMA 0.1 0.001

$SIMULATION (12345) ONLYSIM

$TABLE ID TIME AMT IPRED BMI HT CR AGE GEN WT BSA GFR CV1 CV2 CV3 CV4

NOPRINT FILE = OUT.DAT ONEHEADER