protected override void Context()
{
base.Context();
_simulation = new IndividualSimulation {
DataRepository = new DataRepository()
};
_baseGrid = new BaseGrid("Time", DomainHelperForSpecs.TimeDimensionForSpecs())
{
Values = new[] { 10f, 20f, 30f }
};
_dataColumn1 = new DataColumn("C1", DomainHelperForSpecs.ConcentrationDimensionForSpecs(), _baseGrid)
{
DataInfo = { Origin = ColumnOrigins.Calculation },
QuantityInfo = { Path = new[] { "C1", "Concentration" } },
Values = new[] { 11f, 21f, 31f }
};
_dataColumn2 = new DataColumn("C2", DomainHelperForSpecs.ConcentrationDimensionForSpecs(), _baseGrid)
{
DataInfo = { Origin = ColumnOrigins.Calculation },
QuantityInfo = { Path = new[] { "C2", "Concentration" } },
Values = new[] { 12f, 22f, 32f }
};
_simulation.DataRepository.Add(_dataColumn1);
_simulation.DataRepository.Add(_dataColumn2);
//Setup global PK analysis
_globalPKAnalysis = new GlobalPKAnalysis();
var c1Container = new Container().WithName("C1");
c1Container.Add(DomainHelperForSpecs.ConstantParameterWithValue(0.5).WithName(CoreConstants.PKAnalysis.FractionAbsorbed));
var c2Container = new Container().WithName("C2");
c2Container.Add(DomainHelperForSpecs.ConstantParameterWithValue(1).WithName(CoreConstants.PKAnalysis.FractionAbsorbed));
_globalPKAnalysis.Add(c1Container);
_globalPKAnalysis.Add(c2Container);
_pkC1 = new PKAnalysis
{
DomainHelperForSpecs.ConstantParameterWithValue(1).WithName(Constants.PKParameters.MRT),
DomainHelperForSpecs.ConstantParameterWithValue(2).WithName(Constants.PKParameters.Tmax)
};
_pkC2 = new PKAnalysis
{
DomainHelperForSpecs.ConstantParameterWithValue(3).WithName(Constants.PKParameters.MRT),
DomainHelperForSpecs.ConstantParameterWithValue(4).WithName(Constants.PKParameters.Tmax)
};
A.CallTo(() => _pkMapper.MapFrom(_dataColumn1, A <PKValues> ._, A <PKParameterMode> ._, "C1")).Returns(_pkC1);
A.CallTo(() => _pkMapper.MapFrom(_dataColumn2, A <PKValues> ._, A <PKParameterMode> ._, "C2")).Returns(_pkC2);
_defaultNumberOfRules = DomainHelperForSpecs.ConstantParameterWithValue(3).Rules.Count;
}
protected override void Context()
{
_representationInfoRepository = A.Fake <IRepresentationInfoRepository>();
sut = new GlobalPKAnalysisToDataTableMapper(_representationInfoRepository);
_globalPKAnalysis = new GlobalPKAnalysis();
_compound1 = new Container().WithName("Drug");
_compound2 = new Container().WithName("Inhibitor");
_globalPKAnalysis.Add(_compound1);
_globalPKAnalysis.Add(_compound2);
_compound1.Add(DomainHelperForSpecs.ConstantParameterWithValue(1).WithName("P1"));
_compound1.Add(DomainHelperForSpecs.ConstantParameterWithValue(2).WithName("P2"));
_compound2.Add(DomainHelperForSpecs.ConstantParameterWithValue(3).WithName("P1"));
_compound2.Add(DomainHelperForSpecs.ConstantParameterWithValue(4).WithName("P3"));
A.CallTo(() => _representationInfoRepository.InfoFor(A <IParameter> ._))
.ReturnsLazily(x => new RepresentationInfo {
DisplayName = "Display for " + x.GetArgument <IParameter>(0).Name
});
}
public static GlobalPKAnalysis GenerateGlobalPKAnalysis(string drugName)
{
var globalPKAnalysis = new GlobalPKAnalysis();
var container = new Container().WithName(drugName);
globalPKAnalysis.Add(container);
container.AddChildren(
new PKSimParameter {
Name = Constants.PKParameters.Vd, Value = 0.0
},
new PKSimParameter {
Name = Constants.PKParameters.Vss, Value = 0.0
});
return(globalPKAnalysis);
}
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);
}
