Supplementary Material #2: code for NONMEM

; Base model

$PROB BASE 1

$INPUT SIM ID TIME DOSE LWT DV

$DATA sim2.txt

$PRED

KA=EXP(THETA(1)+ETA(1))

CL=EXP(THETA(2)+ETA(2))

V1=EXP(THETA(3)+ETA(3))

Y=DOSE*KA/(V1*(KA-CL/V1))*(EXP(-TIME*CL/V1)-EXP(-TIME*KA))*(1+EPS(1))

$THETA

2.3 ;1 ~lka

-0.693 ;2 ~lCL

-1.61 ;2 ~lV

$OMEGA 0 FIX 0.1 0.1

$SIGMA 0.4

$EST METHOD=1 INTERACTION PRINT=5 NOABORT

; Covariate model

$PROB COVARIATE 1

$INPUT SIM ID TIME DOSE LWT DV

$DATA sim2.txt

$PRED

KA=EXP(THETA(1)+ETA(1))

CL=EXP(THETA(2))*(EXP(LWT)/70)**THETA(4)*EXP(ETA(2))

V1=EXP(THETA(3)+ETA(3))

Y=DOSE*KA/(V1*(KA-CL/V1))*(EXP(-TIME*CL/V1)-EXP(-TIME*KA))*(1+EPS(1))

$THETA

2.3 ;1 ~lka

-0.693 ;2 ~lCL

-1.61 ;3 ~lV

0.1 ;4 PWT

$OMEGA 0 FIX 0.1 0.1

$SIGMA 0.4

$EST METHOD=1 INTERACTION PRINT=5 NOABORT

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