;; 1. Description: Chloroquine PK model ;;----------------------------------------------------------------------------;; ;; Mahidol-Oxford Tropical Medicine Research Unit ;; Project name: Chloroquine - CQPRQ interactions ;; date: 2020-05-22 ;;----------------------------------------------------------------------------;; $PROBLEM 1 $INPUT ID TIME DV AMT EVID CMT MDV TBW COMED $DATA Simulated_run1.csv IGNORE = @ $SUBROUTINE ADVAN5 TRANS1 $MODEL COMP = (1) ;Absorption compartment COMP = (2) ;CQ COMP = (3) ;CQ peripheral compartment 1 COMP = (4) ;CQ peripheral compartment 2 COMP = (5) ;Transit compartment 1 COMP = (6) ;Transit compartment 2 COMP = (7) ;Transit compartment 3 $PK ;=============== Between-occasion variability - MTT ======================; OCC1 = 0 OCC2 = 0 IF(COMED.EQ.0) OCC1 = 1 IF(COMED.EQ.1) OCC2 = 1 BOVMT = ETA(9)*OCC1 + ETA(10)*OCC2 ;===================================================================; TVCL = THETA(1)*((TBW/61.9)**0.75); ;Typical value CL = TVCL*EXP(ETA(1)) ;Individual parameter estimate TVV2 = THETA(2)*((TBW/61.9)**1.0); ;Typical value V2 = TVV2*EXP(ETA(2)) ;Individual parameter estimate TVMTT = THETA(3); ;Typical value MTT = TVMTT*EXP(ETA(3)+BOVMT) ;Individual parameter estimate TVF1 = THETA(4); ;Typical value F1 = TVF1*EXP(ETA(4)) ;Individual parameter estimate TVQ1 = THETA(5)*((TBW/61.9)**0.75); ;Typical value Q1 = TVQ1*EXP(ETA(5)) ;Individual parameter estimate TVV4 = THETA(6)*((TBW/61.9)**1.0); ;Typical value V4 = TVV4*EXP(ETA(6)) ;Individual parameter estimate TVQ2 = THETA(7)*((TBW/61.9)**0.75); ;Typical value Q2 = TVQ2*EXP(ETA(7)) ;Individual parameter estimate TVV5 = THETA(8)*((TBW/61.9)**1.0); ;Typical value V5 = TVV5*EXP(ETA(8)) ;Individual parameter estimate NN = 3 ; Number of transit compartments KTR = (NN+1)/MTT ;Calculate ktr K15 = KTR ;Transfer between absorption and first transit compartment K56 = KTR ;Transfer between first and second transit compartment K67 = KTR ;Transfer between second and third transit compartment K72 = KTR ;Transfer between thrid transit compartment and central CQ compartment K20 = (CL/V2) ;Elimination of CQ K23 = Q1/V2 ;Distribution into first periferal compartment K32 = Q1/V4 ;Distribution from first periferal compartment K24 = Q2/V2 ;Distribution into second periferal compartment K42 = Q2/V5 ;Distribution from second periferal compartment S2 = V2 ;Scaling factor in central CQ compartment $ERROR IF(CMT.EQ.2) THEN IPRED = A(2)/S2 ;Calculate CQ individual prediction W = SQRT(SIGMA(1,1)) ;Define CQ residuals ENDIF IPRED = LOG(IPRED) ;Calculate logarithmic individual predictions IRES = DV-IPRED IWRES = IRES/W Y = IPRED + EPS(1) $THETA (0, 37.8) ;1.TVCL (0, 2020) ;2.TVV2 (0, 1.26) ;3.TVMTT (1) FIX ;4.TVF1 (0, 20.3) ;5.TVQ1 (0, 6740) ;6.TVV4 (0, 174) ;7.TVQ2 (0, 3270) ;8.TVV5 $OMEGA 0.0236 ;1.IIV CL 0.0685 ;2.IIV V2 0.151 ;3.IIV MTT 0.0111 ;4.IIV F1 0 FIX ;5.IIV Q1 0 FIX ;6.IIV V4 0 FIX ;7.IIV Q2 0 FIX ;8.IIV V5 $OMEGA BLOCK(1) 0.166 ;9-10 BOV-MTT_OCC1 $OMEGA BLOCK(1) SAME $SIGMA 0.0806 ;1.RUV OS $ESTIMATION MAXEVAL=0 PRINT=5 POSTHOC METHOD=1 INTER MCETA=500 NSIG=1