Source code for pkpd.protocols.protocol_pkpd_simulate_liver_flow

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# * Authors:     Carlos Oscar Sorzano (
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# * Kinestat Pharma
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    from itertools import izip
except ImportError:
    izip = zip
import numpy as np
import os

import pyworkflow.protocol.params as params
from .protocol_pkpd import ProtPKPD
from pkpd.objects import PKPDODEModel
from pkpd.biopharmaceutics import DrugSource, createDeltaDose, createVia

[docs]class PKPDLiver(PKPDODEModel):
[docs] def F(self, t, y): Vsys=self.parameters[0] ClNH=self.parameters[1] fb=self.parameters[2] Kp=self.parameters[3] Vinlet=self.parameters[4] Vliver=self.parameters[5] Qh=self.parameters[6] Clint=self.parameters[7] Iliver=y[0] Iinlet=y[1] Isys=y[2] retval = np.array([1/Vliver*(Qh*Iinlet-(Qh+fb*Clint)*Iliver/Kp), Qh/Vinlet*(Isys-Iinlet), 1/Vsys*(Qh*(Iliver/Kp-Isys)-ClNH*Isys)],np.double) return retval
[docs] def G(self, t, dD): Vinlet=self.parameters[4] return np.array([0.0,dD/Vinlet,0.0],np.double)
[docs] def imposeConstraints(self, yt): if yt[0]<0: yt[0]=0 if yt[1]<0: yt[1]=0 if yt[2]<0: yt[2]=0
[docs] def getResponseDimension(self): return 3
[docs] def getStateDimension(self): return 3
[docs]class PKPDLiverEV1(): def __init__(self): self.drugSource = DrugSource() self.model = PKPDLiver() self.model.drugSource = self.drugSource self.via = createVia("Oral; ev1")
[docs] def setTimeRange(self,tF): self.model.t0 = 0 self.model.tF = tF*60
[docs] def setDose(self,doseAmount): self.drugSource.setDoses([createDeltaDose(doseAmount,self.via,0,"mg")],self.model.t0,self.model.tF) self.NparametersSource = len(self.drugSource.getParameterNames())
[docs] def simulate(self,params,t): self.drugSource.setParameters(params[0:self.NparametersSource]) return self.model.forwardModel(params[self.NparametersSource:],t)
[docs]class ProtPKPDSimulateLiverFlow(ProtPKPD): """ Simulate the concentration of a compound (typically an enzyme inhibitor) at liver.\n Protocol created by\n""" _label = 'simulate liver flow' #--------------------------- DEFINE param functions -------------------------------------------- def _defineParams(self, form, fullForm=True): form.addSection('Input') form.addParam('tF', params.FloatParam, default=8, label='Max. simulation time [h]') group = form.addGroup("Absorption") group.addParam("weight", params.StringParam, default=70, label="Weight [kg]") group.addParam("dose", params.StringParam, default=1, label="Dose [mg/kg]") group.addParam("Fa", params.StringParam, default=1, label="Fraction absorbed (0-1)") group.addParam("ka", params.StringParam, default=0.05, label="1st order absorption rate [1/min]", help="Typically between 0.0003 and 0.1") group = form.addGroup("Central compartment") group.addParam("Vsys", params.StringParam, default=200, label="Distribution volume [mL/kg]") group.addParam("ClNH", params.StringParam, default=1, label="Non hepatic clearance [mL/min/kg]", help="Typically between 0.6 and 600") group.addParam("fb", params.StringParam, default=1, label="Unbound fraction in blood [0-1]") group = form.addGroup("Liver") group.addParam("Kp", params.StringParam, default=1, label="Liver-to-blood concentration ratio") group.addParam("Vinlet", params.StringParam, default=1, label="Liver inlet volume [mL/kg]") group.addParam("Vliver", params.StringParam, default=40, label="Liver volume [mL/kg]") group.addParam("Qh", params.StringParam, default=30, label="Liver blood flow [mL/min/kg]") group.addParam("Clint", params.StringParam, default=10, label="Intrinsic metabolic clearance [mL/min/kg]", help="Typically between 3 and 300") #--------------------------- INSERT steps functions -------------------------------------------- def _insertAllSteps(self): self._insertFunctionStep('runSimulate') #--------------------------- STEPS functions --------------------------------------------
[docs] def parseList(self, strList): return [float(v) for v in strList.split(' ')]
[docs] def runSimulate(self): model = PKPDLiverEV1() model.setTimeRange(self.tF.get()) t = np.arange(0.0, self.tF.get()*60, 1) I = [] legends = [] weightList = self.parseList(self.weight.get()) doseList = self.parseList(self.dose.get()) FaList = self.parseList(self.Fa.get()) kaList = self.parseList(self.ka.get()) VsysList = self.parseList(self.Vsys.get()) ClNHList = self.parseList(self.ClNH.get()) fbList = self.parseList(self.fb.get()) KpList = self.parseList(self.Kp.get()) VinletList = self.parseList(self.Vinlet.get()) VliverList = self.parseList(self.Vliver.get()) QhList = self.parseList(self.Qh.get()) ClintList = self.parseList(self.Clint.get()) for weight in weightList: for dose in doseList: for Fa in FaList: for ka in kaList: for Vsys in VsysList: for ClNH in ClNHList: for fb in fbList: for Kp in KpList: for Vinlet in VinletList: for Vliver in VliverList: for Qh in QhList: for Clint in ClintList: legend="Weight=%f Dose=%f Fa=%f ka=%f Vsys=%f ClNH=%f fb=%f Kp=%f Vinlet=%f Vliver=%f Qh=%f Clint=%f"%\ (weight, dose, Fa, ka, Vsys, ClNH, fb, Kp, Vinlet, Vliver, Qh, Clint) print("Simulating %s"%legend) legends.append(legend) model.setDose(Fa*dose*weight) Ii = model.simulate([ka,Vsys*weight,ClNH*weight,fb,Kp, Vinlet*weight,Vliver*weight,Qh*weight*model.model.deltaT, Clint*weight],t) I.append((t,Ii)) if len(I)>0: fh=open(self._getPath("profiles.txt"),'w') fhSummary=open(self._getPath("summary.txt"),"w") for toPlot, legend in izip(I,legends): fh.write("SimulateLiver::"+legend+"\n") fhSummary.write("Simulated %s\n"%(legend)) t, I3 = toPlot for n in range(t.size): fh.write("%f %f %f %f\n"%(t[n],I3[0][n],I3[1][n],I3[2][n])) fh.write("\n") fh.close() fhSummary.close()
#--------------------------- INFO functions -------------------------------------------- def _summary(self): msg=[] if os.path.exists(self._getPath("summary.txt")): fh=open(self._getPath("summary.txt")) for line in fh: msg.append(line.strip()) fh.close() return msg def _citations(self): retval = ['Kanamitsu2000'] return retval