private void setSingleDosingPKValues(ICache <string, double> pk, DosingInterval interval, double?dose)
{
setCmaxAndTmax(pk, interval, dose, Constants.PKParameters.C_max, Constants.PKParameters.Tmax);
setValue(pk, Constants.PKParameters.C_tEnd, interval.CTrough);
setValueAndNormalize(pk, Constants.PKParameters.AUC, interval.Auc, dose);
setValueAndNormalize(pk, Constants.PKParameters.AUC_inf, interval.AucInf, dose);
setFirstIntervalPKValues(pk, interval, dose);
setValue(pk, Constants.PKParameters.FractionAucEndToInf, interval.FractionAucEndToInf);
}
private void setFirstIntervalPKValues(ICache <string, double> pk, DosingInterval interval, double?dose)
{
setValue(pk, Constants.PKParameters.Thalf, interval.Thalf);
setValue(pk, Constants.PKParameters.MRT, interval.Mrt);
if (!dose.HasValue)
{
return;
}
setValue(pk, Constants.PKParameters.CL, interval.CL);
setValue(pk, Constants.PKParameters.Vss, interval.Vss);
setValue(pk, Constants.PKParameters.Vd, interval.Vd);
}
private PKInterval pkIntervalFromDosingInterval(DosingInterval dosingInterval, List <float> time, List <float> concentration, PKCalculationOptions options)
{
if (dosingInterval == null)
{
return(null);
}
var dosingStartIndex = ArrayHelper.ClosestIndexOf(time, dosingInterval.StartValue);
var dosingEndIndex = ArrayHelper.ClosestIndexOf(time, dosingInterval.EndValue);
if (oneTimeIndexInvalid(dosingStartIndex, dosingEndIndex))
{
return(null);
}
return(createPKInterval(time, concentration, dosingStartIndex, dosingEndIndex, options, dosingInterval.DrugMassPerBodyWeight));
}
private IEnumerable <DosingInterval> allIntervalsFor(IReadOnlyList <float> time, IReadOnlyList <float> concentration, PKCalculationOptions options)
{
var timeValues = time.ToList();
var concentrationValues = concentration.ToList();
if (!timeValues.Any() || !concentrationValues.Any())
{
yield break;
}
var fullRange = new DosingInterval(timeValues, concentrationValues, options);
//only one interval
if (options.SingleDosing)
{
yield return(fullRange);
yield break;
}
var firstDosingStartIndex = ArrayHelper.ClosestIndexOf(timeValues, options.FirstDosingStartValue);
var firstDosingEndIndex = ArrayHelper.ClosestIndexOf(timeValues, options.FirstDosingEndValue);
var lastMinusOneDosingStartIndex = ArrayHelper.ClosestIndexOf(timeValues, options.LastMinusOneDosingStartValue);
var lastDosingStartIndex = ArrayHelper.ClosestIndexOf(timeValues, options.LastDosingStartValue);
var lastDosingEndIndex = ArrayHelper.ClosestIndexOf(timeValues, options.LastDosingEndValue);
if (oneTimeIndexInvalid(firstDosingEndIndex, firstDosingStartIndex, lastDosingStartIndex, lastDosingEndIndex, lastMinusOneDosingStartIndex))
{
yield break;
}
yield return(dosingInterval(timeValues, concentrationValues, firstDosingStartIndex, firstDosingEndIndex, options));
//The end time of the last minus one dosing interval is the start time of the last interval
yield return(dosingInterval(timeValues, concentrationValues, lastMinusOneDosingStartIndex, lastDosingStartIndex, options));
yield return(dosingInterval(timeValues, concentrationValues, lastDosingStartIndex, lastDosingEndIndex, options));
yield return(fullRange);
}
public PKCalculationOptions CreateFor(IModelCoreSimulation simulation, string moleculeName)
{
var options = new PKCalculationOptions();
var endTime = (simulation.EndTime ?? 0).ToFloat();
var allApplicationParameters = simulation.AllApplicationParametersOrderedByStartTimeFor(moleculeName);
// all application start times starting before the end of the simulation
var applicationStartTimes = allApplicationParameters.Select(x => x.StartTime.Value).ToFloatArray();
var applicationEndTimes = new List <float>(applicationStartTimes.Skip(1))
{
endTime
};
for (int i = 0; i < applicationStartTimes.Length; i++)
{
var dosingInterval = new DosingInterval
{
StartValue = applicationStartTimes[i],
EndValue = applicationEndTimes[i]
};
options.AddInterval(dosingInterval);
}
// single dosing
if (applicationStartTimes.Length <= 1)
{
options.InfusionTime = allApplicationParameters.FirstOrDefault()?.InfusionTime?.Value;
}
// Once all dosing are defined, update total drug mass
UpdateTotalDrugMassPerBodyWeight(simulation, moleculeName, options, allApplicationParameters);
return(options);
}
private void setCmaxAndTmax(ICache <string, double> pk, DosingInterval interval, double?dose, string cmaxName, string tMaxName)
{
setValueAndNormalize(pk, cmaxName, interval.Cmax, dose);
setValue(pk, tMaxName, interval.Tmax);
}
public virtual void AddInterval(DosingInterval dosingInterval) => _dosingIntervals.Add(dosingInterval);
