def po_bolus(simulator, r):
""" Oral bolus dose
oral dose (single dose, at given start with given dose).
Examples are the oral glucose tolerance test (OGTT) or the application of a drug orally,
e.g., codeine, midazolam, caffeine or paracetamol.
:return:
"""
# set initial concentration of somatostatin in all blood compartments
changes_init = pkpd.init_concentrations_changes(r, 'som', 0E-6) # [0 nmol/L]
# oral bolus dose
# FIXME: dosing changesets
changes_po_bolus = {
'PODOSE_som': 10.0E-6, # [mg]
}
# simulate
tcsims = ensemble(
TimecourseSim([
Timecourse(start=0, end=1200, steps=600,
changes={
**changes_init,
**changes_po_bolus}
)
]),
changeset=ChangeSet.parameter_sensitivity_changeset(r, 0.1)
)
return simulator.timecourses(tcsims)
def stepped_clamp(simulator, r):
changes_init = pkpd.init_concentrations_changes(r, 'som', 0E-6) # [0 nmol/L]
tcsims = ensemble(
TimecourseSim([
Timecourse(start=0, end=60, steps=120, changes=changes_init),
Timecourse(start=0, end=60, steps=120, changes={'Ri_som': 10.0E-6}), # [mg/min],
Timecourse(start=0, end=60, steps=120, changes={'Ri_som': 20.0E-6}), # [mg/min],
Timecourse(start=0, end=60, steps=120, changes={'Ri_som': 40.0E-6}), # [mg/min],
Timecourse(start=0, end=60, steps=120, changes={'Ri_som': 80.0E-6}), # [mg/min],
]), ChangeSet.parameter_sensitivity_changeset(r, 0.1)
)
return simulator.timecourses(tcsims)
def mix(simulator, r):
"""
[5] combination experiments
- somatostatin infusion + c-peptide bolus
- hyperinsulinemic, euglycemic clamp
"""
changes_init = pkpd.init_concentrations_changes(r, 'som', 0E-6) # [0 nmol/L]
tcsims = ensemble(
TimecourseSim([
Timecourse(start=0, end=60, steps=120, changes=changes_init),
Timecourse(start=0, end=60, steps=120, changes={'IVDOSE_som': 10.0E-6}),
Timecourse(start=0, end=60, steps=240, changes={'Ri_som': 10.0E-6}), # [mg/min],
Timecourse(start=0, end=60, steps=120, changes={'Ri_som': 10.0E-6, 'PODOSE_som': 10.0E-4}),
Timecourse(start=0, end=120, steps=240, changes={'Ri_som': 0.0}), # [mg/min],
]), ChangeSet.parameter_sensitivity_changeset(r, 0.1))
return simulator.timecourses(tcsims)
def iv_infusion(simulator, r):
""" [3] constant infusion (for given period, tstart, tend)
- somatostatin infusion
- insulin infusion
- glucose infusion
- glucagon infusion
:return:
"""
changes_init = pkpd.init_concentrations_changes(r, 'som', 0E-6) # [0 nmol/L]
tcsims = ensemble(
TimecourseSim([
Timecourse(start=0, end=60, steps=120, changes=changes_init),
Timecourse(start=0, end=120, steps=240, changes={'Ri_som': 10.0E-6}), # [mg/min],
Timecourse(start=0, end=120, steps=240, changes={'Ri_som': 0.0}), # [mg/min],
]), ChangeSet.parameter_sensitivity_changeset(r, 0.1)
)
return simulator.timecourses(tcsims)
def clamp(simulator, r):
"""
clamping of substance (e.g. glucose, tstart, tend)
- glucose clamping (euglycemic clamp)
- insulin clamping (insulin clamp)
:return:
"""
changes_init = pkpd.init_concentrations_changes(r, 'som', 0E-6) # [0 nmol/L]
# FIXME: some bug in the concentrations and assignments
tcsims = ensemble(
TimecourseSim([
Timecourse(start=0, end=60, steps=120, changes={**changes_init, **{'PODOSE_som': 1E-9}}),
Timecourse(start=0, end=120, steps=240, model_changes={'boundary_condition': {"Ave_som": True}}), # clamp venous som
Timecourse(start=0, end=120, steps=240, model_changes={'boundary_condition': {"Ave_som": False}}), # release venous som,
]), ChangeSet.parameter_sensitivity_changeset(r, 0.1)
)
return simulator.timecourses(tcsims)
def iv_bolus(simulator, r):
""" [2] bolus injection (at given time tstart, with given dose and given injection time, e.g. 5-10 min)
- c-peptide bolus
- ivGTT (glucose bolus)
- insulin injection
"""
changes_init = pkpd.init_concentrations_changes(r, 'som', 0E-6) # [0 nmol/L]
changes_iv_bolus = {
'IVDOSE_som': 10E-6, # [mg]
}
p_changeset = ChangeSet.parameter_sensitivity_changeset(r, 0.1)
tcsims = ensemble(
TimecourseSim([
Timecourse(start=0, end=1200, steps=600,
changes={
**changes_init,
**changes_iv_bolus}
)
]), p_changeset)
return simulator.timecourses(tcsims)