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Copy pathsystem-glp_study.txt
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125 lines (109 loc) · 3.93 KB
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#
# Units:
#
# mass [=] nmoles
# volume [=] L
# concentration [=] nM
# time [=] hours
#
# Parameters for NHP parameters were taken from:
#
# Betts A, Keunecke A, van Steeg TJ, et al. Linear pharmacokinetic parameters
# for monoclonal antibodies are similar within a species and across different
# pharmacological targets: A comparison between human, cynomolgus monkey and
# hFcRn Tg32 transgenic mouse using a population-modeling approach. MAbs.
# 2018;10(5):751-764.
#
# Human estimates for absorption was taken from:
#
# Dirks, N.L. & Meibohm, B. Clin Pharmacokinet (2010) 49: 633. https://doi.org/10.2165/11535960-000000000-00000
#
# The population estimate was 0.217/day or 0.00904/hour
#
#
#
#-------------#
# Parameters #
#-------------#
#
# name value lower upper units editable grouping
# bound bound
<P> BW 3.0 eps Inf kg yes System
<P> BW_R 3.0 eps Inf kg no System
<P> MW 145.0 eps Inf kDa yes System
<P> CL 0.00015 eps Inf L/hr/kg yes System
<P> Q 0000029 eps Inf L/hr/kg yes System
<P> Vp 0.04589 eps Inf L/kg yes System
<P> Vt 0.03114 eps Inf L/kg yes System
<P> ka 0.10 eps Inf 1/hr yes System
<P> Fb 0.74 eps Inf 1/hr yes System
<PSET:default> NHP
<PSET:human> Human
<PSET:human:BW> 70
<PSET:human:ka> 0.00904
<PSET:human:Fb> 1.0
# Scaling the clearances:
<As> CL_AL = CL*BW_R*SIMINT_POWER[BW/BW_R][0.75]/BW
<As> Q_AL = Q*BW_R*SIMINT_POWER[BW/BW_R][0.75]/BW
<As> kel = CL_AL/Vp
<As> kpt = Q_AL/Vp
<As> ktp = Q_AL/Vt
<As> Beta_hr = 0.5*(kpt + ktp + kel - SIMINT_POWER[SIMINT_POWER[kpt + ktp + kel][2.0] - 4.0*ktp*kel][0.5])
<As> Thalf_days = SIMINT_LOGN[2.0]/Beta_hr/24.0
#--------------------#
# Dosing information #
#--------------------#
#
# Dosing times in weeks ==> days
# dosing magnitude in mpk ==> nM
#
# Basis: 70 kg human
# mAb with MW of 150 KDA
#
# mg 1e6 ng 1nmoles 1 1e3 nmoles
# X -- x ------- x ----------------- x ------ = X * ------------
# kg 1 mg MW (kDa)*1e3 ng Vp (L) MW(kDa) Vp(L)
#
#
#
# Bolus Events
# times/events state values scale units
<B:times>; [ 0 ]; 24; days
<B:events>; Cp ; [ 0 ]; 1e3/MW/Vp; mg/kg
<B:events>; At ; [ 0 ]; 1e3/MW; mg/kg
#------------------#
# Rate Information #
#------------------#
#---------------------------------------------------------------------------#
# PK
<ODE:At> -ka*At
<ODE:Cp> ka*Fb*At/Vp
Ct; Vt; ktp <C> Cp; Vp; kpt
<S:Cp> kel*Cp
#---------------------------------------------------------------------------#
#----------#
# Outputs #
#----------#
# Convert ng/ml to nM
#
# ng 1000 ml nmoles
# X -- x ------- x --------------- = X/MW (KDA)
# ml 1L MW (KDA)*1000 ng
#
# Convert from nM to ng/ml:
#
# X nM ===> X*MW(KDA) ng/ml
#
<O> Cp_nM = Cp
<O> Cp_ngml = Cp*MW
#---------#
# Options #
#---------#
# specify different time scales
<TS:hours> 1.0
<TS:days> 1.0/24.0
<TS:weeks> 1.0/24.0/7.0
# output times
<OPT:output_times> SIMINT_SEQ[0][2*7*24][10]
# default time scale
<OPT:TS> days