public IEnumerable <PopulationPKAnalysis> CalculateFor(IPopulationDataCollector populationDataCollector, ChartData <TimeProfileXValue, TimeProfileYValue> timeProfileChartData)
{
var pkAnalyses = new List <PopulationPKAnalysis>();
if (timeProfileChartData == null)
{
return(pkAnalyses); // there are no analyses to calculate
}
var allColumns = timeProfileChartData.Panes.SelectMany(x => x.Curves).Select(x =>
new { curveData = x, column = columnFor(x, populationDataCollector) })
.Where(c => c.column != null)
.Where(c => c.column.IsConcentration());
var columnsByMolecules = allColumns.GroupBy(x => x.column.MoleculeName());
foreach (var columnsByMolecule in columnsByMolecules)
{
var moleculeName = columnsByMolecule.Key;
var options = _pkCalculationOptionsFactory.CreateFor(populationDataCollector, moleculeName);
pkAnalyses.AddRange(columnsByMolecule.Select(pkAnalysisData => new PopulationPKAnalysis(pkAnalysisData.curveData, calculatePKFor(pkAnalysisData.column, moleculeName, options).PKAnalysis)));
}
return(pkAnalyses);
}
protected virtual PopulationSimulationPKAnalyses CalculateFor(ISimulation simulation, int numberOfIndividuals, SimulationResults runResults, Action <int> performIndividualScalingAction)
{
_lazyLoadTask.Load(simulation);
var popAnalyses = new PopulationSimulationPKAnalyses();
foreach (var selectedQuantityForMolecule in simulation.OutputSelections.GroupBy(moleculeNameFrom))
{
var moleculeName = selectedQuantityForMolecule.Key;
var pkCalculationOptions = _pkCalculationOptionsFactory.CreateFor(simulation, moleculeName);
var allApplicationParameters = _pkCalculationOptionsFactory.AllApplicationParametersOrderedByStartTimeFor(simulation, moleculeName);
foreach (var selectedQuantity in selectedQuantityForMolecule)
{
addPKParametersForOutput(simulation, numberOfIndividuals, runResults, performIndividualScalingAction, selectedQuantity, popAnalyses, moleculeName, pkCalculationOptions, allApplicationParameters);
}
}
return(popAnalyses);
}
public GlobalPKAnalysis CalculateGlobalPKAnalysisFor(IEnumerable <Simulation> simulations)
{
var globalPKAnalysis = new GlobalPKAnalysis();
var allSimulations = simulations.ToList();
if (allSimulations.Count != 1)
{
return(globalPKAnalysis);
}
var simulation = allSimulations[0] as IndividualSimulation;
if (simulation == null)
{
return(globalPKAnalysis);
}
//one container per compound
foreach (var compound in simulation.Compounds)
{
var compoundName = compound.Name;
var container = new Container().WithName(compoundName);
globalPKAnalysis.Add(container);
var peripheralVenousBloodCurve = simulation.DataRepository.PeripheralVenousBloodColumn(compoundName);
var venousBloodCurve = simulation.DataRepository.VenousBloodColumn(compoundName);
if (peripheralVenousBloodCurve == null || venousBloodCurve == null)
{
continue;
}
var options = _pkCalculationOptionsFactory.CreateFor(simulation, compoundName);
var venousBloodPlasmaPK = _pkAnalysisTask.CalculatePK(venousBloodCurve, options);
var aucIV = simulation.AucIVFor(compoundName);
var aucDDI = simulation.AucDDIFor(compoundName);
var cmaxDDI = simulation.CmaxDDIFor(compoundName);
var bioAvailability = createRatioParameter(CoreConstants.PKAnalysis.Bioavailability, venousBloodPlasmaPK[Constants.PKParameters.AUC_inf], aucIV, Constants.Dimension.DIMENSIONLESS);
var bioAvailabilityValue = bioAvailability.Value;
var bloodCurveForPKAnalysis = bloodCurveForSpecies(peripheralVenousBloodCurve, venousBloodCurve, simulation.Individual);
var bloodPlasmaPK = _pkAnalysisTask.CalculatePK(bloodCurveForPKAnalysis, options);
var applicationType = applicationTypeFor(simulation, compound);
var aucRatio = createRatioParameter(CoreConstants.PKAnalysis.AUCRatio, bloodPlasmaPK[pkParameterNameForAUCRatio(applicationType)], aucDDI, Constants.Dimension.DIMENSIONLESS);
var cmaxRatio = createRatioParameter(CoreConstants.PKAnalysis.C_maxRatio, bloodPlasmaPK[pkParameterNameForCmaxRatio(applicationType)], cmaxDDI, Constants.Dimension.DIMENSIONLESS);
var vssPlasma = createParameter(CoreConstants.PKAnalysis.VssPlasma, bloodPlasmaPK[Constants.PKParameters.Vss], CoreConstants.Dimension.VolumePerBodyWeight);
var vssPlasmaOverF = createParameter(CoreConstants.PKAnalysis.VssPlasmaOverF, bloodPlasmaPK[Constants.PKParameters.Vss], CoreConstants.Dimension.VolumePerBodyWeight);
var vdPlasma = createParameter(CoreConstants.PKAnalysis.VdPlasma, bloodPlasmaPK[Constants.PKParameters.Vd], CoreConstants.Dimension.VolumePerBodyWeight);
var vdPlasmaOverF = createParameter(CoreConstants.PKAnalysis.VdPlasmaOverF, bloodPlasmaPK[Constants.PKParameters.Vd], CoreConstants.Dimension.VolumePerBodyWeight);
var vssPhysChem = createParameter(CoreConstants.PKAnalysis.VssPhysChem, calculateVSSPhysChemFor(simulation, compoundName), CoreConstants.Dimension.VolumePerBodyWeight);
var totalPlasmaCL = createParameter(CoreConstants.PKAnalysis.TotalPlasmaCL, bloodPlasmaPK[Constants.PKParameters.CL], CoreConstants.Dimension.FlowPerWeight);
var totalPlasmaCLOverF = createParameter(CoreConstants.PKAnalysis.TotalPlasmaCLOverF, bloodPlasmaPK[Constants.PKParameters.CL], CoreConstants.Dimension.FlowPerWeight);
if (_interactionTask.HasInteractionInvolving(compound, simulation))
{
container.AddChildren(aucRatio, cmaxRatio);
}
var fractionAbsorbed = fractionAbsorbedFor(simulation, compoundName);
//multiple application or no application? in that case, only show fraction absorbed for oral
if (applicationType != ApplicationType.Single)
{
if (isMultipleOral(simulation, compound))
{
container.Add(fractionAbsorbed);
}
continue;
}
var schemaItem = singleDosingItem(simulation, compound);
var pkValues = new List <IParameter>();
var bioAvailabilityCalculated = !double.IsNaN(bioAvailabilityValue);
if (isIntravenous(schemaItem))
{
container.AddChildren(vssPlasma, vdPlasma, vssPhysChem, totalPlasmaCL);
continue;
}
var fractionAbsorbedWarningParameters = new List <IParameter>();
if (bioAvailabilityCalculated)
{
vssPlasma.Value *= bioAvailabilityValue;
vdPlasma.Value *= bioAvailabilityValue;
totalPlasmaCL.Value *= bioAvailabilityValue;
fractionAbsorbedWarningParameters.AddRange(new[] { vssPlasma, vdPlasma });
pkValues.AddRange(new[] { vssPlasma, vdPlasma, totalPlasmaCL, bioAvailability });
}
else
{
fractionAbsorbedWarningParameters.AddRange(new[] { vssPlasmaOverF, vdPlasmaOverF });
pkValues.AddRange(new[] { vssPlasmaOverF, vdPlasmaOverF, totalPlasmaCLOverF, bioAvailability });
}
if (isOral(schemaItem))
{
fractionAbsorbed.Rules.Add(fractionAbsorbedRule);
pkValues.Add(fractionAbsorbed);
if (bioAvailability.Value > fractionAbsorbed.Value)
{
bioAvailability.Rules.Add(bioAvailabilityRule);
}
addFractionAbsorvedWarningTo(fractionAbsorbed, fractionAbsorbedWarningParameters);
}
container.AddChildren(pkValues);
}
return(globalPKAnalysis);
}