// (WARNING: DO NOT EDIT) Machine generated by pbpk2cpp.cpp on Sat Mar 08 15:12:11 2008

// Title: PBPk of Diazepam, (Oral: 2mg) (vs Friedman1992, 2mg)

#include <stdlib.h>
#include <stdio.h> 
#include <math.h>  
#include <string.h>
#include <time.h>  

// global constants
const  double  global_totalVolume  = 70000.0 ;
const  double  global_totalFlow  = (6000.0 / 60.0) ;
const  double  global_startTime  = 0 ;
const  double  global_stopTime  = (13 * 3600) ;
const  double  global_dTime  = 1.0 ;

// substance constants
const  double  diazepam_blood2PlasmaRatio  = 0.57 ;
const  double  diazepam_siinternalTransitRate  = (41.9e-5) ;
const  double  diazepam_siabsorptionRate  = (49.7e-5) ;

// compartment constants
const  double  venousBlood_volume  = 0.0557 * global_totalVolume ;
const  double  arterialBlood_volume  = 0.0243 * global_totalVolume ;
const  double  rest_volume  = 0.1347 * global_totalVolume ;
const  double  rest_bloodFlow  = 0.08 ;
const  double  adiposeTissue_volume  = 0.25 * global_totalVolume ;
const  double  adiposeTissue_bloodFlow  = 0.10 ;
const  double  skin_volume  = 0.0371 * global_totalVolume ;
const  double  skin_bloodFlow  = 0.05 ;
const  double  muscle_volume  = 0.4143 * global_totalVolume ;
const  double  muscle_bloodFlow  = 0.17 ;
const  double  gastrointestinalTract_volume  = 0.0214 * global_totalVolume ;
const  double  gastrointestinalTract_bloodFlow  = 0.190 ;
const  double  kidneys_volume  = 0.0044 * global_totalVolume ;
const  double  kidneys_bloodFlow  = 0.19 ;
const  double  liver_volume  = 0.0257 * global_totalVolume ;
const  double  liver_bloodFlow  = 0.060 ;
const  double  liver_bloodFlowOutput  = 0.25 ;
const  double  heart_volume  = 0.0047 * global_totalVolume ;
const  double  heart_bloodFlow  = 0.04 ;
const  double  brain_volume  = 0.02 * global_totalVolume ;
const  double  brain_bloodFlow  = 0.120 ;
const  double  lungs_volume  = 0.0077 * global_totalVolume ;

// compartment substance variables and constants
double  venousBlood_diazepam_amount = 0.0 ;
const  double  venousBlood_diazepam_rateConstant  = (global_totalFlow) / venousBlood_volume ;
double  arterialBlood_diazepam_amount = 0.0 ;
const  double  arterialBlood_diazepam_rateConstant  = (global_totalFlow) / arterialBlood_volume ;
double  rest_diazepam_amount = 0.0 ;
const  double  rest_diazepam_partitionCoefficientBlood  = 0.07 ;
const  double  rest_diazepam_rateConstant  = (rest_bloodFlow *  global_totalFlow) / (rest_volume * rest_diazepam_partitionCoefficientBlood) ;
double  adiposeTissue_diazepam_amount = 0.0 ;
const  double  adiposeTissue_diazepam_partitionCoefficientBlood  = 4.4 ;
const  double  adiposeTissue_diazepam_rateConstant  = (adiposeTissue_bloodFlow *  global_totalFlow) / (adiposeTissue_volume * adiposeTissue_diazepam_partitionCoefficientBlood) ;
double  skin_diazepam_amount = 0.0 ;
const  double  skin_diazepam_partitionCoefficientBlood  = 0.80 ;
const  double  skin_diazepam_rateConstant  = (skin_bloodFlow *  global_totalFlow) / (skin_volume * skin_diazepam_partitionCoefficientBlood) ;
double  muscle_diazepam_amount = 0.0 ;
const  double  muscle_diazepam_partitionCoefficientBlood  = 0.38 ;
const  double  muscle_diazepam_rateConstant  = (muscle_bloodFlow *  global_totalFlow) / (muscle_volume * muscle_diazepam_partitionCoefficientBlood) ;
double  gastrointestinalTract_diazepam_amount = 0.0 ;
const  double  gastrointestinalTract_diazepam_partitionCoefficientBlood  = 0.69 ;
const  double  gastrointestinalTract_diazepam_rateConstant  = (gastrointestinalTract_bloodFlow *  global_totalFlow) / (gastrointestinalTract_volume * gastrointestinalTract_diazepam_partitionCoefficientBlood) ;
double  colon_diazepam_amount = 0.0 ;
double  smallIntestine5_diazepam_amount = 0.0 ;
const  double  smallIntestine5_diazepam_internalTransitRateConstant  = (diazepam_siinternalTransitRate) ;
const  double  smallIntestine5_diazepam_absorptionRateConstant  = (diazepam_siabsorptionRate     ) ;
double  smallIntestine4_diazepam_amount = 0.0 ;
const  double  smallIntestine4_diazepam_internalTransitRateConstant  = (diazepam_siinternalTransitRate) ;
const  double  smallIntestine4_diazepam_absorptionRateConstant  = (diazepam_siabsorptionRate     ) ;
double  smallIntestine3_diazepam_amount = 0.0 ;
const  double  smallIntestine3_diazepam_internalTransitRateConstant  = (diazepam_siinternalTransitRate) ;
const  double  smallIntestine3_diazepam_absorptionRateConstant  = (diazepam_siabsorptionRate     ) ;
double  smallIntestine2_diazepam_amount = 0.0 ;
const  double  smallIntestine2_diazepam_internalTransitRateConstant  = (diazepam_siinternalTransitRate) ;
const  double  smallIntestine2_diazepam_absorptionRateConstant  = (diazepam_siabsorptionRate     ) ;
double  smallIntestine1_diazepam_amount = 0.0 ;
const  double  smallIntestine1_diazepam_internalTransitRateConstant  = (diazepam_siinternalTransitRate) ;
const  double  smallIntestine1_diazepam_absorptionRateConstant  = (diazepam_siabsorptionRate     ) ;
double  stomach_diazepam_amount = 0.0 ;
const  double  stomach_diazepam_gastricEmptyingRateConstant  = (167e-5) ;
double  kidneys_diazepam_amount = 0.0 ;
const  double  kidneys_diazepam_partitionCoefficientBlood  = 0.7 ;
const  double  kidneys_diazepam_rateConstant  = (kidneys_bloodFlow *  global_totalFlow) / (kidneys_volume * kidneys_diazepam_partitionCoefficientBlood) ;
double  liver_diazepamExcreted_amount = 0.0 ;
double  liver_diazepam_amount = 0.0 ;
const  double  liver_diazepam_partitionCoefficientBlood  = 0.84 ;
const  double  liver_diazepam_clearanceBlood  = 0.9747 ;
const  double  liver_diazepam_rateConstant  = (liver_bloodFlowOutput * global_totalFlow) / (liver_volume * liver_diazepam_partitionCoefficientBlood) ;
const  double  liver_diazepam_excretionRatio  = liver_diazepam_clearanceBlood / liver_volume ;
double  heart_diazepam_amount = 0.0 ;
const  double  heart_diazepam_partitionCoefficientBlood  = 0.9 ;
const  double  heart_diazepam_rateConstant  = (heart_bloodFlow *  global_totalFlow) / (heart_volume * heart_diazepam_partitionCoefficientBlood) ;
double  brain_diazepam_amount = 0.0 ;
const  double  brain_diazepam_partitionCoefficientBlood  = 0.35 ;
const  double  brain_diazepam_rateConstant  = (brain_bloodFlow *  global_totalFlow) / (brain_volume * brain_diazepam_partitionCoefficientBlood) ;
double  lungs_diazepam_amount = 0.0 ;
const  double  lungs_diazepam_partitionCoefficientBlood  = 0.59 ;
const  double  lungs_diazepam_rateConstant  = (global_totalFlow) / (lungs_volume * lungs_diazepam_partitionCoefficientBlood) ;


void  InjectSubstance (double  currentTime)
{
    static  int  finished = 0;
    if (finished) {
        return;    
    } /* if */     
    if (currentTime >= 0) {
        stomach_diazepam_amount += 2.0e6;
        finished = 1;    
    } /* if */     

}

void  PlotPhysiology (double  currentTime)
{
    static  double  nextPlot = 0.0;
    if (currentTime >= nextPlot) {
        nextPlot += 60;    
        printf("%g ",currentTime / 3600.0);
        printf("%g ",brain_diazepam_amount / brain_volume);
        printf("%g ",kidneys_diazepam_amount / kidneys_volume);
        printf("%g ",adiposeTissue_diazepam_amount / adiposeTissue_volume);
        printf("%g ",venousBlood_diazepam_amount / (venousBlood_volume * diazepam_blood2PlasmaRatio ));   // convert Cbloodtotal to Cplasma
        printf("\n");
        printf("# diazepamTotal: %g\n",stomach_diazepam_amount + colon_diazepam_amount + smallIntestine1_diazepam_amount  + smallIntestine2_diazepam_amount  + smallIntestine3_diazepam_amount  + smallIntestine4_diazepam_amount  + smallIntestine5_diazepam_amount + lungs_diazepam_amount  + brain_diazepam_amount + heart_diazepam_amount + liver_diazepam_amount + liver_diazepamExcreted_amount + kidneys_diazepam_amount + gastrointestinalTract_diazepam_amount + muscle_diazepam_amount + skin_diazepam_amount + adiposeTissue_diazepam_amount + rest_diazepam_amount + arterialBlood_diazepam_amount + venousBlood_diazepam_amount);
    } /* if */     
}

void  ProcessPhysiologyTop (double  currentTime)  // Eulers
{
    double  venousBlood_diazepam_dAmount = 0.0;
    double  arterialBlood_diazepam_dAmount = 0.0;
    double  rest_diazepam_dAmount = 0.0;
    double  adiposeTissue_diazepam_dAmount = 0.0;
    double  skin_diazepam_dAmount = 0.0;
    double  muscle_diazepam_dAmount = 0.0;
    double  gastrointestinalTract_diazepam_dAmount = 0.0;
    double  colon_diazepam_dAmount = 0.0;
    double  smallIntestine5_diazepam_dAmount = 0.0;
    double  smallIntestine4_diazepam_dAmount = 0.0;
    double  smallIntestine3_diazepam_dAmount = 0.0;
    double  smallIntestine2_diazepam_dAmount = 0.0;
    double  smallIntestine1_diazepam_dAmount = 0.0;
    double  stomach_diazepam_dAmount = 0.0;
    double  kidneys_diazepam_dAmount = 0.0;
    double  liver_diazepamExcreted_dAmount = 0.0;
    double  liver_diazepam_dAmount = 0.0;
    double  heart_diazepam_dAmount = 0.0;
    double  brain_diazepam_dAmount = 0.0;
    double  lungs_diazepam_dAmount = 0.0;

    venousBlood_diazepam_dAmount = -(venousBlood_diazepam_rateConstant * venousBlood_diazepam_amount)  + (rest_diazepam_rateConstant * rest_diazepam_amount)  + (adiposeTissue_diazepam_rateConstant * adiposeTissue_diazepam_amount)  + (skin_diazepam_rateConstant * skin_diazepam_amount)  + (muscle_diazepam_rateConstant * muscle_diazepam_amount)  + (kidneys_diazepam_rateConstant * kidneys_diazepam_amount)  + (liver_diazepam_rateConstant * liver_diazepam_amount)  + (heart_diazepam_rateConstant * heart_diazepam_amount)  + (brain_diazepam_rateConstant * brain_diazepam_amount) ;
    arterialBlood_diazepam_dAmount = -(arterialBlood_diazepam_rateConstant * arterialBlood_diazepam_amount)  + (lungs_diazepam_rateConstant * lungs_diazepam_amount) ;
    rest_diazepam_dAmount = -(rest_diazepam_rateConstant * rest_diazepam_amount)  + (rest_bloodFlow * arterialBlood_diazepam_rateConstant * arterialBlood_diazepam_amount) ;
    adiposeTissue_diazepam_dAmount = -(adiposeTissue_diazepam_rateConstant * adiposeTissue_diazepam_amount)  + (adiposeTissue_bloodFlow * arterialBlood_diazepam_rateConstant * arterialBlood_diazepam_amount) ;
    skin_diazepam_dAmount = -(skin_diazepam_rateConstant * skin_diazepam_amount)  + (skin_bloodFlow * arterialBlood_diazepam_rateConstant * arterialBlood_diazepam_amount) ;
    muscle_diazepam_dAmount = -(muscle_diazepam_rateConstant * muscle_diazepam_amount)  + (muscle_bloodFlow * arterialBlood_diazepam_rateConstant * arterialBlood_diazepam_amount) ;
    gastrointestinalTract_diazepam_dAmount = -(gastrointestinalTract_diazepam_rateConstant * gastrointestinalTract_diazepam_amount)  + (smallIntestine1_diazepam_absorptionRateConstant * smallIntestine1_diazepam_amount)  + (smallIntestine2_diazepam_absorptionRateConstant * smallIntestine2_diazepam_amount)  + (smallIntestine3_diazepam_absorptionRateConstant * smallIntestine3_diazepam_amount)  + (smallIntestine4_diazepam_absorptionRateConstant * smallIntestine4_diazepam_amount)  + (smallIntestine5_diazepam_absorptionRateConstant * smallIntestine5_diazepam_amount)  + (gastrointestinalTract_bloodFlow * arterialBlood_diazepam_rateConstant * arterialBlood_diazepam_amount) ;
    colon_diazepam_dAmount = (smallIntestine5_diazepam_internalTransitRateConstant * smallIntestine5_diazepam_amount) ;
    smallIntestine5_diazepam_dAmount = -(smallIntestine5_diazepam_internalTransitRateConstant * smallIntestine5_diazepam_amount) - (smallIntestine5_diazepam_absorptionRateConstant * smallIntestine5_diazepam_amount) + (smallIntestine4_diazepam_internalTransitRateConstant * smallIntestine4_diazepam_amount) ;
    smallIntestine4_diazepam_dAmount = -(smallIntestine4_diazepam_internalTransitRateConstant * smallIntestine4_diazepam_amount) - (smallIntestine4_diazepam_absorptionRateConstant * smallIntestine4_diazepam_amount) + (smallIntestine3_diazepam_internalTransitRateConstant * smallIntestine3_diazepam_amount) ;
    smallIntestine3_diazepam_dAmount = -(smallIntestine3_diazepam_internalTransitRateConstant * smallIntestine3_diazepam_amount) - (smallIntestine3_diazepam_absorptionRateConstant * smallIntestine3_diazepam_amount) + (smallIntestine2_diazepam_internalTransitRateConstant * smallIntestine2_diazepam_amount) ;
    smallIntestine2_diazepam_dAmount = -(smallIntestine2_diazepam_internalTransitRateConstant * smallIntestine2_diazepam_amount) - (smallIntestine2_diazepam_absorptionRateConstant * smallIntestine2_diazepam_amount) + (smallIntestine1_diazepam_internalTransitRateConstant * smallIntestine1_diazepam_amount) ;
    smallIntestine1_diazepam_dAmount = -(smallIntestine1_diazepam_internalTransitRateConstant * smallIntestine1_diazepam_amount) - (smallIntestine1_diazepam_absorptionRateConstant * smallIntestine1_diazepam_amount) + (stomach_diazepam_gastricEmptyingRateConstant * stomach_diazepam_amount) ;
    stomach_diazepam_dAmount = -(stomach_diazepam_gastricEmptyingRateConstant * stomach_diazepam_amount) ;
    kidneys_diazepam_dAmount = -(kidneys_diazepam_rateConstant * kidneys_diazepam_amount)  + (kidneys_bloodFlow * arterialBlood_diazepam_rateConstant * arterialBlood_diazepam_amount) ;
    liver_diazepamExcreted_dAmount = (liver_diazepam_excretionRatio * liver_diazepam_amount) ;
    liver_diazepam_dAmount = -(liver_diazepam_rateConstant * liver_diazepam_amount)  - (liver_diazepam_excretionRatio * liver_diazepam_amount)  + (liver_bloodFlow * arterialBlood_diazepam_rateConstant * arterialBlood_diazepam_amount)  + (gastrointestinalTract_diazepam_rateConstant * gastrointestinalTract_diazepam_amount) ;
    heart_diazepam_dAmount = -(heart_diazepam_rateConstant * heart_diazepam_amount)  + (heart_bloodFlow * arterialBlood_diazepam_rateConstant * arterialBlood_diazepam_amount) ;
    brain_diazepam_dAmount = -(brain_diazepam_rateConstant * brain_diazepam_amount)  + (brain_bloodFlow * arterialBlood_diazepam_rateConstant * arterialBlood_diazepam_amount) ;
    lungs_diazepam_dAmount = -(lungs_diazepam_rateConstant * lungs_diazepam_amount)  + (venousBlood_diazepam_rateConstant * venousBlood_diazepam_amount) ;

    venousBlood_diazepam_amount += venousBlood_diazepam_dAmount * global_dTime ;
    arterialBlood_diazepam_amount += arterialBlood_diazepam_dAmount * global_dTime ;
    rest_diazepam_amount += rest_diazepam_dAmount * global_dTime ;
    adiposeTissue_diazepam_amount += adiposeTissue_diazepam_dAmount * global_dTime ;
    skin_diazepam_amount += skin_diazepam_dAmount * global_dTime ;
    muscle_diazepam_amount += muscle_diazepam_dAmount * global_dTime ;
    gastrointestinalTract_diazepam_amount += gastrointestinalTract_diazepam_dAmount * global_dTime ;
    colon_diazepam_amount += colon_diazepam_dAmount * global_dTime ;
    smallIntestine5_diazepam_amount += smallIntestine5_diazepam_dAmount * global_dTime ;
    smallIntestine4_diazepam_amount += smallIntestine4_diazepam_dAmount * global_dTime ;
    smallIntestine3_diazepam_amount += smallIntestine3_diazepam_dAmount * global_dTime ;
    smallIntestine2_diazepam_amount += smallIntestine2_diazepam_dAmount * global_dTime ;
    smallIntestine1_diazepam_amount += smallIntestine1_diazepam_dAmount * global_dTime ;
    stomach_diazepam_amount += stomach_diazepam_dAmount * global_dTime ;
    kidneys_diazepam_amount += kidneys_diazepam_dAmount * global_dTime ;
    liver_diazepamExcreted_amount += liver_diazepamExcreted_dAmount * global_dTime ;
    liver_diazepam_amount += liver_diazepam_dAmount * global_dTime ;
    heart_diazepam_amount += heart_diazepam_dAmount * global_dTime ;
    brain_diazepam_amount += brain_diazepam_dAmount * global_dTime ;
    lungs_diazepam_amount += lungs_diazepam_dAmount * global_dTime ;
}


void  RunSimulation ()
{
    double  currentTime;

    for (currentTime = global_startTime; currentTime < global_stopTime; currentTime += global_dTime) {
        InjectSubstance(currentTime) ;
        ProcessPhysiologyTop(currentTime) ;
        PlotPhysiology(currentTime) ;
    } /* currentTimeForLoop */ 
}

void main ()
{
    RunSimulation();
}