protected override void Context()
{
base.Context();
_simulation = A.Fake <ISimulation>();
_runResults = A.Fake <SimulationResults>();
var outputSelections = new OutputSelections();
outputSelections.AddOutput(new QuantitySelection("Liver|Cell|Drug|Concentration", QuantityType.Drug));
A.CallTo(() => _simulation.OutputSelections).Returns(outputSelections);
var pKCalculationOptions = new PKCalculationOptions();
A.CallTo(_pkCalculationOptionsFactory).WithReturnType <PKCalculationOptions>().Returns(pKCalculationOptions);
_p1 = new PKParameter {
Name = "AUC", Mode = PKParameterMode.Single
};
_userDefinedParameter1 = new UserDefinedPKParameter {
Name = "Dynamic1", Mode = PKParameterMode.Single
};
A.CallTo(() => _pkParameterRepository.All()).Returns(new[] { _p1, _userDefinedParameter1 });
var individualResults = A.Fake <IndividualResults>();
A.CallTo(() => _runResults.AllIndividualResults).Returns(new HashSet <IndividualResults>(new[] { individualResults }));
var pKValues = new PKValues();
pKValues.AddValue(_p1.Name, 10f);
pKValues.AddValue(_userDefinedParameter1.Name, 30f);
A.CallTo(_pkValuesCalculator).WithReturnType <PKValues>().Returns(pKValues);
}
protected override void Context()
{
base.Context();
_simulation = A.Fake <ISimulation>();
_runResults = A.Fake <SimulationResults>();
var outputSelections = new OutputSelections();
outputSelections.AddOutput(new QuantitySelection("Liver|Cell|Drug|Concentration", QuantityType.Drug));
A.CallTo(() => _simulation.OutputSelections).Returns(outputSelections);
var pKCalculationOptions = new PKCalculationOptions();
A.CallTo(_pkCalculationOptionsFactory).WithReturnType <PKCalculationOptions>().Returns(pKCalculationOptions);
_p1 = new PKParameter().WithName("AUC");
_p1.Mode = PKParameterMode.Single;
_p2 = new PKParameter().WithName("AUC" + Constants.PKParameters.NormSuffix);
_p2.Mode = PKParameterMode.Single;
A.CallTo(() => _pkParameterRepository.All()).Returns(new[] { _p1, _p2 });
var individualResults = A.Fake <IndividualResults>();
A.CallTo(() => _runResults.AllIndividualResults).Returns(new HashSet <IndividualResults>(new[] { individualResults }));
var pKValues = new PKValues();
pKValues.AddValue(_p1.Name, 10f);
pKValues.AddValue(_p2.Name, 20f);
A.CallTo(_pkValuesCalculator).WithReturnType <PKValues>().Returns(pKValues);
}
protected override void Context()
{
sut = new UserDefinedPKParameter();
_options = new PKCalculationOptions {
TotalDrugMassPerBodyWeight = 20
};
_interval0 = new DosingInterval {
DrugMassPerBodyWeight = 2
};
_interval1 = new DosingInterval {
DrugMassPerBodyWeight = 3
};
_interval2 = new DosingInterval {
DrugMassPerBodyWeight = 4
};
_interval3 = new DosingInterval {
DrugMassPerBodyWeight = 5
};
_interval4 = new DosingInterval {
DrugMassPerBodyWeight = 6
};
_options.AddInterval(_interval0);
_options.AddInterval(_interval1);
_options.AddInterval(_interval2);
_options.AddInterval(_interval3);
_options.AddInterval(_interval4);
}
public override void GlobalContext()
{
base.GlobalContext();
_singleDosing = DataColumnLoader.GetDataColumnFrom("SingleDosing_CL");
_pkOptions = new PKCalculationOptions
{
Dose = 10,
};
}
public override void GlobalContext()
{
base.GlobalContext();
_singleDosing = DataColumnLoader.GetDataColumnFrom("SingleDosing_CL");
_pkOptions = new PKCalculationOptions
{
TotalDrugMassPerBodyWeight = 10,
};
}
public override void GlobalContext()
{
base.GlobalContext();
_multipleDosingColumn = DataColumnLoader.GetDataColumnFrom("MultipleDosing_0_8_16");
_pkOptions = new PKCalculationOptions
{
TotalDrugMassPerBodyWeight = 10,
};
_pkOptions.AddInterval(new DosingInterval {
StartValue = 0, EndValue = 8, DrugMassPerBodyWeight = _firstDose
});
_pkOptions.AddInterval(new DosingInterval {
StartValue = 8, EndValue = 16, DrugMassPerBodyWeight = _oneMinusLastDose
});
_pkOptions.AddInterval(new DosingInterval {
StartValue = 16, EndValue = 48, DrugMassPerBodyWeight = _lastDose
});
_cmax_tD1_tD2 = new UserDefinedPKParameter {
StartApplicationIndex = 0, EndApplicationIndex = 1, StandardPKParameter = StandardPKParameter.C_max, Name = "MyCmaxD1D2"
};
_cmax_tD1_tD2_DOSE_BW = new UserDefinedPKParameter {
StartApplicationIndex = 0, EndApplicationIndex = 1, StandardPKParameter = StandardPKParameter.C_max, Name = "MyCmaxD1D2_Normalized", NormalizationFactor = _firstDose
};
_cmax_tD1_tD2_DOSE_BW_auto = new UserDefinedPKParameter {
StartApplicationIndex = 0, EndApplicationIndex = 1, StandardPKParameter = StandardPKParameter.C_max_norm, Name = "MyCmaxD1D2_Normalized_auto"
};
_tmax_tD1_tD2 = new UserDefinedPKParameter {
StartApplicationIndex = 0, EndApplicationIndex = 1, StandardPKParameter = StandardPKParameter.t_max, Name = "MyTmaxD1D2"
};
_cmax_t1_t2 = new UserDefinedPKParameter {
StartTime = 0, EndTime = 8, StandardPKParameter = StandardPKParameter.C_max, Name = "MyCmaxT1T2"
};
_cmax_t1_t2_offset = new UserDefinedPKParameter {
StartTime = 0, StartTimeOffset = 16, EndTime = 48, StandardPKParameter = StandardPKParameter.C_max, Name = "MyCmaxT1T2offset"
};
_cmax_t1_offset_no_end = new UserDefinedPKParameter {
StartTime = 0, StartTimeOffset = 16, StandardPKParameter = StandardPKParameter.C_max, Name = "MyCmaxT1offset_no_end"
};
_tThreshold = new UserDefinedPKParameter {
StartApplicationIndex = 0, StandardPKParameter = StandardPKParameter.Tthreshold, Name = "Threshold", ConcentrationThreshold = 4
};
_tThreshold_last = new UserDefinedPKParameter {
StartApplicationIndex = 2, StandardPKParameter = StandardPKParameter.Tthreshold, Name = "Threshold_last", ConcentrationThreshold = 5
};
_allDynamicPkParameters = new[] { _cmax_tD1_tD2, _tmax_tD1_tD2, _cmax_t1_t2, _cmax_t1_t2_offset, _cmax_t1_offset_no_end, _cmax_tD1_tD2_DOSE_BW, _tThreshold, _tThreshold_last, _cmax_tD1_tD2_DOSE_BW_auto };
}
protected override void Context()
{
base.Context();
_baseGrid = new BaseGrid("BaseGrid", Constants.Dimension.NO_DIMENSION)
{
Values = new float[0]
};
_emptyColums = new DataColumn("TEST", Constants.Dimension.NO_DIMENSION, _baseGrid)
{
Values = new float[0]
};
_pkOptions = new PKCalculationOptions
{
Dose = 10,
};
}
public double?EstimateDrugMassPerBodyWeight(PKCalculationOptions pkCalculationOptions)
{
// It can be quite complicated to estimate the total drug mass between two intervals
// If a start time and end time is provided or any time offset, we cannot calculate for sure and we'll return NULL
// if a start application and an end infusion index is provided, we'll sum up the interval between those two application
// if a start application is provided, we'll sum up the drug mass starting at this application until the end
// if an end application is provided, we'll sum up the drug mass from the start until the application
if (StartTime.HasValue || EndTime.HasValue || EndTimeOffset.HasValue || StartTimeOffset.HasValue)
{
return(null);
}
//no intervals defined
if (!StartApplicationIndex.HasValue && !EndApplicationIndex.HasValue)
{
return(pkCalculationOptions.TotalDrugMassPerBodyWeight);
}
var startApplicationIndex = StartApplicationIndex.GetValueOrDefault(0);
var endApplicationIndex = EndApplicationIndex.GetValueOrDefault(pkCalculationOptions.DosingIntervals.Count);
// invalid intervals
if (startApplicationIndex >= endApplicationIndex)
{
return(null);
}
double drugMassPerBodyWeight = 0;
for (int applicationIndex = startApplicationIndex; applicationIndex < endApplicationIndex; applicationIndex++)
{
//wrong indexes
var interval = pkCalculationOptions.DosingIntervalAt(applicationIndex);
if (interval == null)
{
return(null);
}
drugMassPerBodyWeight += interval.DrugMassPerBodyWeight.GetValueOrDefault(0);
}
return(drugMassPerBodyWeight);
}
public override void GlobalContext()
{
base.GlobalContext();
_multipleDosingColumn = DataColumnLoader.GetDataColumnFrom("MultipleDosing_0_8_16");
_pkOptions = new PKCalculationOptions
{
FirstDosingStartValue = 0,
FirstDosingEndValue = 8,
LastMinusOneDosingStartValue = 8,
LastDosingStartValue = 16,
LastDosingEndValue = 48,
Dose = 10,
FirstDose = 4,
LastMinusOneDose = 4,
LastDose = 2
};
}
public override void GlobalContext()
{
base.GlobalContext();
_multipleDosingColumn = DataColumnLoader.GetDataColumnFrom("MultipleDosing_0_8_16");
_pkOptions = new PKCalculationOptions
{
TotalDrugMassPerBodyWeight = 10,
};
_pkOptions.AddInterval(new DosingInterval {
StartValue = 0, EndValue = 8, DrugMassPerBodyWeight = _firstDose
});
_pkOptions.AddInterval(new DosingInterval {
StartValue = 8, EndValue = 16, DrugMassPerBodyWeight = _oneMinusLastDose
});
_pkOptions.AddInterval(new DosingInterval {
StartValue = 16, EndValue = 48, DrugMassPerBodyWeight = _lastDose
});
}
private IndividualPKAnalysis calculatePKFor(DataColumn dataColumn, string moleculeName, PKCalculationOptions options, GlobalPKAnalysis globalPKAnalysis = null)
{
var timeValue = dataColumn.BaseGrid.Values;
var dimension = _dimensionRepository.MergedDimensionFor(dataColumn);
var umolPerLiterUnit = dimension.UnitOrDefault(CoreConstants.Units.MicroMolPerLiter);
var concentrationValueInMolL = dataColumn.Values.Select(v => dimension.BaseUnitValueToUnitValue(umolPerLiterUnit, v)).ToArray();
var pkAnalysis = _pkMapper.MapFrom(dataColumn, _pkValuesCalculator.CalculatePK(timeValue, concentrationValueInMolL, options), options.PKParameterMode, moleculeName);
addWarningsTo(pkAnalysis, globalPKAnalysis, moleculeName);
return(new IndividualPKAnalysis(dataColumn, pkAnalysis));
}
public PKValues CalculatePK(DataColumn column, PKCalculationOptions options)
{
return(_pkValuesCalculator.CalculatePK(column, options));
}
protected override void Because()
{
_options = sut.CreateFor(_simulation1, _moleculeName);
}
protected override void Because()
{
_result = sut.CreateFor(_simulation1, _secondMetaboliteName);
}
protected override void Because()
{
_result = sut.CreateFor(_populationSimulation, _appliedCompound);
}
public override bool PKParameterCanBeUsed(PKParameter pkParameter, PKCalculationOptions pkCalculationOptions)
{
return(base.PKParameterCanBeUsed(pkParameter, pkCalculationOptions) && !isNormParameter(pkParameter));
}
public override void UpdateAppliedDose(ISimulation simulation, string moleculeName, PKCalculationOptions options, IReadOnlyList <ApplicationParameters> allApplicationParameters)
{
base.UpdateAppliedDose(simulation, moleculeName, options, allApplicationParameters);
if (options.SingleDosing)
{
return;
}
//we have at least 2 applied applications at that stage since we are in multiple dosing mode
var bodyWeight = simulation.DowncastTo <Simulation>().BodyWeight?.Value;
var applicationCount = allApplicationParameters.Count;
options.FirstDose = drugMassPerBodyWeightFor(allApplicationParameters[0].DrugMass, bodyWeight);
options.LastMinusOneDose = drugMassPerBodyWeightFor(allApplicationParameters[applicationCount - 2].DrugMass, bodyWeight);
options.LastDose = drugMassPerBodyWeightFor(allApplicationParameters[applicationCount - 1].DrugMass, bodyWeight);
}
