Jones2013: Jones2013 Human PBPK RxODE model

In nlmixrdevelopment/rxModels: RxODE model library

Description

Jones2013 Human PBPK RxODE model

Usage

Jones2013

Format

An RxODE model with 53 parameters, 16 ODE states, and 1 calc vars.

Parameters (Jones2013$params)

BW

(default=70)

FVad

(default=0.213)

FVbo

(default=0.085629)

FVbr

(default=0.02)

FVgu

(default=0.0171)

FVhe

(default=0.0047)

FVki

(default=0.0044)

FVli

(default=0.021)

FVlu

(default=0.0076)

FVmu

(default=0.4)

FVsk

(default=0.0371)

FVsp

(default=0.0026)

FVte

(default=0.01)

FVve

(default=0.0514)

FVar

(default=0.0257)

FVpl

(default=0.0424)

FVrb

(default=0.0347)

FVre

(default=0.099771)

FQad

(default=0.05)

FQbo

(default=0.05)

FQbr

(default=0.12)

FQgu

(default=0.146462)

FQhe

(default=0.04)

FQki

(default=0.19)

FQh

(default=0.215385)

FQlu

(default=1)

FQmu

(default=0.17)

FQsk

(default=0.05)

FQsp

(default=0.017231)

FQte

(default=0.01076)

FQre

(default=0.103855)

Kpad

(default=0.191)

Kpbo

(default=0.374)

Kpbr

(default=0.606)

Kpgu

(default=0.578)

Kphe

(default=0.583)

Kpki

(default=0.597)

Kpli

(default=0.57)

Kplu

(default=0.62)

Kpmu

(default=0.622)

Kpsk

(default=0.6)

Kpsp

(default=0.591)

Kpte

(default=0.6)

Kpre

(default=0.6)

fup

(default=0.681)

BP

(default=0.98)

fumic

(default=1)

HLM_CLint

(default=8)

CLrenal

(default=0)

Ka

(default=2.18)

F

(default=1)

CO

(default=108.33)

MPPGL

(default=45)

State Jones2013$state

Aad

(=1)

Abo

(=2)

Abr

(=3)

Agu

(=4)

Ahe

(=5)

Aki

(=6)

Ali

(=7)

Alu

(=8)

Amu

(=9)

Ask

(=10)

Asp

(=11)

Ate

(=12)

Ave

(=13)

Aar

(=14)

Are

(=15)

D

(=16)

Calculated Variables Jones2013$lhs

Cp

Concentration in plasma

Model Code

RxODE( BW = 70 FVad = 0.213 FVbo = 0.085629 FVbr = 0.02 FVgu = 0.0171 FVhe = 0.0047 FVki = 0.0044 FVli = 0.021 FVlu = 0.0076 FVmu = 0.4 FVsk = 0.0371 FVsp = 0.0026 FVte = 0.01 FVve = 0.0514 FVar = 0.0257 FVpl = 0.0424 FVrb = 0.0347 FVre = 0.099771 FQad = 0.05 FQbo = 0.05 FQbr = 0.12 FQgu = 0.146462 FQhe = 0.04 FQki = 0.19 FQh = 0.215385 FQlu = 1 FQmu = 0.17 FQsk = 0.05 FQsp = 0.017231 FQte = 0.01076 FQre = 0.103855 Kpad = 0.191 Kpbo = 0.374 Kpbr = 0.606 Kpgu = 0.578 Kphe = 0.583 Kpki = 0.597 Kpli = 0.57 Kplu = 0.62 Kpmu = 0.622 Kpsk = 0.6 Kpsp = 0.591 Kpte = 0.6 Kpre = 0.6 fup = 0.681 BP = 0.98 fumic = 1 HLM_CLint = 8 CLrenal = 0 Ka = 2.18 F = 1 CO = 108.33 Vad ~ BW * FVad Vbo ~ BW * FVbo Vbr ~ BW * FVbr Vgu ~ BW * FVgu Vhe ~ BW * FVhe Vki ~ BW * FVki Vli ~ BW * FVli Vlu ~ BW * FVlu Vmu ~ BW * FVmu Vsk ~ BW * FVsk Vsp ~ BW * FVsp Vte ~ BW * FVte Vve ~ BW * FVve Var ~ BW * FVar Vpl ~ BW * FVpl Vrb ~ BW * FVrb Vre ~ BW * FVre Vplas_ven ~ Vpl * Vve/(Vve + Var) Vplas_art ~ Vpl * Var/(Vve + Var) QC ~ CO/1000 * 60 * 60 Qad ~ QC * FQad Qbo ~ QC * FQbo Qbr ~ QC * FQbr Qgu ~ QC * FQgu Qhe ~ QC * FQhe Qki ~ QC * FQki Qh ~ QC * FQh Qha ~ Qh - Qgu - Qsp Qlu ~ QC * FQlu Qmu ~ QC * FQmu Qsk ~ QC * FQsk Qsp ~ QC * FQsp Qte ~ QC * FQte Qre ~ QC * FQre Cadipose ~ Aad/Vad Cbone ~ Abo/Vbo Cbrain ~ Abr/Vbr Cgut ~ Agu/Vgu Cheart ~ Ahe/Vhe Ckidney ~ Aki/Vki Cliver ~ Ali/Vli Clung ~ Alu/Vlu Cmuscle ~ Amu/Vmu Cskin ~ Ask/Vsk Cspleen ~ Asp/Vsp Ctestes ~ Ate/Vte Cvenous ~ Ave/Vve Carterial ~ Aar/Var Crest ~ Are/Vre Absorption ~ Ka * D * F Cliverfree ~ Cliver * fup Ckidneyfree ~ Ckidney * fup MPPGL = 45 CLmet ~ (HLM_CLint/fumic) * MPPGL * Vli * 60/1000 Venous ~ Qad * (Cadipose/Kpad * BP) + Qbo * (Cbone/Kpbo * BP) + Qbr * (Cbrain/Kpbr * BP) + Qhe * (Cheart/Kphe * BP) + Qki * (Ckidney/Kpki * BP) + Qh * (Cliver/Kpli * BP) + Qmu * (Cmuscle/Kpmu * BP) + Qsk * (Cskin/Kpsk * BP) + Qte * (Ctestes/Kpte * BP) + Qre * (Crest/Kpre * BP) d/dt(Aad) ~ Qad * (Carterial - Cadipose/Kpad * BP) d/dt(Abo) ~ Qbo * (Carterial - Cbone/Kpbo * BP) d/dt(Abr) ~ Qbr * (Carterial - Cbrain/Kpbr * BP) d/dt(Agu) ~ Absorption + Qgu * (Carterial - Cgut/Kpgu * BP) d/dt(Ahe) ~ Qhe * (Carterial - Cheart/Kphe * BP) d/dt(Aki) ~ Qki * (Carterial - Ckidney/Kpki * BP) - CLrenal * Ckidneyfree d/dt(Ali) ~ Qha * Carterial + Qgu * (Cgut/Kpgu * BP) + Qsp * (Cspleen/Kpsp * BP) - Qh * (Cliver/Kpli * BP) - Cliverfree * CLmet d/dt(Alu) ~ Qlu * Cvenous - Qlu * (Clung/Kplu * BP) d/dt(Amu) ~ Qmu * (Carterial - Cmuscle/Kpmu * BP) d/dt(Ask) ~ Qsk * (Carterial - Cskin/Kpsk * BP) d/dt(Asp) ~ Qsp * (Carterial - Cspleen/Kpsp * BP) d/dt(Ate) ~ Qte * (Carterial - Ctestes/Kpte * BP) d/dt(Ave) ~ Venous - Qlu * Cvenous d/dt(Aar) ~ Qlu * (Clung/Kplu * BP) - Qlu * Carterial d/dt(Are) ~ Qre * (Carterial - Crest/Kpre * BP) d/dt(D) ~ -Absorption Cvenous ~ Ave/Vve Cp = Cvenous/BP )

References

Jones H, Rowland-Yeo K. Basic concepts in physiologically based pharmacokinetic modeling in drug discovery and development. CPT Pharmacometrics Syst Pharmacol. 2013 Aug 14;2:e63. doi: 10.1038/psp.2013.41. PubMed PMID: 23945604; PubMed Central PMCID: PMC3828005.

https://github.com/metrumresearchgroup/mrgsolve/blob/9ff7240da48ec133635a6f0db2143f13623f0aff/inst/models/pbpk.cpp

See Also

eventTable, et, rxSolve, RxODE

Examples

Jones2013 %>% solve(et(amt=100,cmt=D,ii=4,until=24) %>% et(seq(0,24,length.out=100))) %>% plot

nlmixrdevelopment/rxModels documentation built on March 26, 2021, 9:17 a.m.