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{"sheet":"PKPD_delay","index":0,"n_rows":29,"n_cols":4,"rows_kept":29,"cut":false,"hidden":false,"merged":[]}
["Name","Parameter","Units","Description"]
["CL",3,"L/h","Clearance"]
["V",35,"L","Volume of distribution"]
["InfusionDuration",0,"h","Infusion duration"]
["Emax",100,"unit","Maximum drug effect"]
["C50",10,"mg/L","Drug conc at 50% of Emax"]
["Hill",1,".","Steepness (Hill exponent)"]
["ThalfDelay",1,"h","Effect compartment elimination half-life"]
["EndEffect",50,"unit","Effect at duration of effect"]
[]
[null,"Dosing"]
["Dose",3500,"mg","Drug dose"]
["DosingInterval",6,"h"]
["Ndoses",1,"."]
[]
[null,"Calculated"]
["ThalfElimination",{"$f":"LN(2)*V/CL","v":8.0867171065326939},"h","Elimination half-life"]
["Duration",{"$f":"EffectDuration(Time,Effect,EndEffect,COUNT(Time))","v":24.75},"h","Duration of effect"]
[]
[]
[]
[]
[]
[]
[]
[]
[]
["Time course of delayed effect because of drug distribution to effect site; Ce=concentration at effect site"]
["Holford NH, Sheiner LB. Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clin Pharmacokinet. 1981;6(6):429-53."]

{"sheet":"Calc","index":1,"n_rows":243,"n_cols":15,"rows_kept":243,"cut":false,"hidden":false,"merged":[]}
["Time","Ndose","TAD","AFk","AFkeq","Conc","Ce","Immediate","Effect",null,"Nick Holford","n.holford@auckland.ac.nz",null,null,"2021-03-04"]
[0,{"$f":"IF((IF(Time=0,1,IF(MOD(Time,DosingInterval)=0,0,1))+INT(Time/DosingInterval))>Ndoses,Ndoses,(IF(Time=0,1,IF(MOD(Time,DosingInterval)=0,0,1))+INT(Time/DosingInterval)))","v":1},{"$f":"(Time-(Ndose-1)*DosingInterval)","v":0},{"$f":"(1-EXP(-Ndose*k*DosingInterval))/(1-EXP(-k*DosingInterval))","v":1},{"$f":"(1-EXP(-Ndose*keq*DosingInterval))/(1-EXP(-keq*DosingInterval))","v":1},{"$f":"IF((Time-(Ndose-1)*DosingInterval)<=tk0,k0/CL*AFk*(1-EXP(-k*TAD)),k0/CL*AFk*(1-EXP(-k*tk0))*EXP(-k*(TAD-tk0)))","v":0},{"$f":"k0*keq/V*((EXP(k*IF(TAD<=tk0,TAD,tk0))-1)*AFk*EXP(-k*TAD)/(k*(keq-k))+(EXP(keq*IF(TAD<=tk0,TAD,tk0))-1)*AFkeq*EXP(-keq*TAD)/(keq*(k-keq)))","v":0},{"$f":"IF(Conc<=0,0,Emax/(1+(Conc/_C50)^(-Hill)))","v":0},{"$f":"IF(Ce<=0,0,Emax/(1+(Ce/_C50)^(-Hill)))","v":0},null,"Protection password",null,"pkpdrx"]
[1E-3,1,1E-3,1,1,99.995714408163138,3.4648362758166198E-2,90.908736714147963,0.34528726374466201]
[{"$f":"IF(Ndoses=1,delta1,0.5)","v":0.25},1,0.25,1,1,97.884133895818863,15.707756932093099,90.730796421226529,61.101234828013411]
[{"$f":"IF(Ndoses=1,A4+delta1,A4+0.5)","v":0.5},1,0.5,1,1,95.808930471003791,28.611872188375884,90.549001907981264,74.101229924275714]
[{"$f":"IF(Ndoses=1,A5+delta1,A5+deltan)","v":0.75},1,0.75,1,1,93.777722626299266,39.136337596624188,90.364020575003622,79.648462850257232,null,"tk0",{"$f":"IF(InfusionDuration<0.001,0.001,InfusionDuration)","v":1E-3},null,"Infusion duration"]
[{"$f":"IF(Ndoses=1,A6+delta1,A6+deltan)","v":1},1,1,1,1,91.789577628535071,47.666687225237624,90.175811479940108,82.658965719772553,null,"k0",{"$f":"Dose/tk0","v":3500000},"mg/h","Infusion rate"]
[{"$f":"IF(Ndoses=1,A7+delta1,A7+deltan)","v":1.25},1,1.25,1,1,89.843582519053896,54.526968513223714,89.984333747147318,84.502603747841235]
[{"$f":"IF(Ndoses=1,A8+delta1,A8+deltan)","v":1.5},1,1.5,1,1,87.938843694479587,59.989528125111612,89.789546595837891,85.71214827720479,null,"k",{"$f":"LN(2)/ThalfElimination","v":8.5714285714285729E-2},"1/h","Elimination rate constant"]
[{"$f":"IF(Ndoses=1,A9+delta1,A9+deltan)","v":1.75},1,1.75,1,1,86.074486496373396,64.28324077529804,89.591409369252816,86.538013291249158,null,"keq",{"$f":"IF(ThalfDelay<0.1,LN(2)/0.1,LN(2)/ThalfDelay)","v":0.69314718055994529},"1/h","Effect compartment rate constant"]
[{"$f":"IF(Ndoses=1,A10+delta1,A10+deltan)","v":2},1,2,1,1,84.249654809589657,67.600428752368629,89.389881564868588,87.113473261969872]
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[{"$f":"IF(Ndoses=1,A12+delta1,A12+deltan)","v":2.5},1,2.5,1,1,80.715233875432389,71.925743139977101,88.976493172324595,87.793824484552857,null,"deltan",0.5,"h","time step for multiple doses"]
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