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Mendez_Catala

Notes


Mendez-Catala, D. M., et al. (2021) Human PBK for oral absorption (administration → blood) with 7 SI boxes + Rest Parent only, perfusion-limited tissues

Overview

key value
Modelled species/orgamism(s) http://purl.obolibrary.org/obo/NCBITaxon_9606
Model chemical(s) http://purl.obolibrary.org/obo/CHEBI_10106
Input route(s) no routes detected
Time resolution h
Amounts unit mg
Volume unit L
Number of compartments 14
Number of species 20
Number of parameters 87 (38 external / 49 internal)

Diagram

Diagram

Compartments

id name unit model qualifier
Stomach Stomach compartment L http://purl.obolibrary.org/obo/PBPKO_00566
SI1 Small intestine compartment L http://purl.obolibrary.org/obo/PBPKO_00472
SI2 Small intestine compartment L http://purl.obolibrary.org/obo/PBPKO_00472
SI3 Small intestine compartment L http://purl.obolibrary.org/obo/PBPKO_00472
SI4 Small intestine compartment L http://purl.obolibrary.org/obo/PBPKO_00472
SI5 Small intestine compartment L http://purl.obolibrary.org/obo/PBPKO_00472
SI6 Small intestine compartment L http://purl.obolibrary.org/obo/PBPKO_00472
SI7 Small intestine compartment L http://purl.obolibrary.org/obo/PBPKO_00472
LI1 Large intestine compartment L http://purl.obolibrary.org/obo/PBPKO_00474
SITissue Small intestine tissue compartment L not specified
Liver Liver compartment L http://purl.obolibrary.org/obo/PBPKO_00558
Blood Blood compartment L http://purl.obolibrary.org/obo/PBPKO_00464
Rest Rest of body compartment L http://purl.obolibrary.org/obo/PBPKO_00450
Feaces Feces compartment L http://purl.obolibrary.org/obo/PBPKO_00555

Species

id name unit model qualifier
ASt Amount in stomach mg not specified
ASI1 Amount in small intestine mg not specified
ASI2 Amount in small intestine mg not specified
ASI3 Amount in small intestine mg not specified
ASI4 Amount in small intestine mg not specified
ASI5 Amount in small intestine mg not specified
ASI6 Amount in small intestine mg not specified
ASI7 Amount in small intestine mg not specified
ALI1 Amount in large intestine mg not specified
ASITissue Amount in small intestine tissue mg not specified
ALiver Amount in liver mg http://purl.obolibrary.org/obo/PBPKO_00497
ABlood Amount in blood mg http://purl.obolibrary.org/obo/PBPKO_00623
ARest Amount in rest of body mg http://purl.obolibrary.org/obo/PBPKO_00501
AFeaces Amount in feces mg http://purl.obolibrary.org/obo/PBPKO_00273
ASITissueMet1 Amount of metabolite in small intestine tissue mg not specified
ALI1Met2 Amount of metabolite in large intestine mg not specified
ALI1Met3 Amount of metabolite in large intestine mg not specified
ALiverMet2 Amount of metabolite in liver mg http://purl.obolibrary.org/obo/PBPKO_00497
ALiverMet3 Amount of metabolite in liver mg http://purl.obolibrary.org/obo/PBPKO_00497
ALiverMet1 Amount of metabolite in liver mg http://purl.obolibrary.org/obo/PBPKO_00497

Transfer equations

id from to equation
_J0 ASt ASI1 ksto * ASt
_J1 ASI1 ASI2 kt1 * ASI1
_J2 ASI2 ASI3 kt2 * ASI2
_J3 ASI3 ASI4 kt3 * ASI3
_J4 ASI4 ASI5 kt4 * ASI4
_J5 ASI5 ASI6 kt5 * ASI5
_J6 ASI6 ASI7 kt6 * ASI6
_J7 ASI7 ALI1 kt7 * ASI7
_J8 ASI1 ASITissue kabsSI1 * CSI1
_J9 ASI2 ASITissue kabsSI2 * CSI2
_J10 ASI3 ASITissue kabsSI3 * CSI3
_J11 ASI4 ASITissue kabsSI4 * CSI4
_J12 ASI5 ASITissue kabsSI5 * CSI5
_J13 ASI6 ASITissue kabsSI6 * CSI6
_J14 ASI7 ASITissue kabsSI7 * CSI7
_J15 ALI1 ALiver kabsLI * CLI1
_J16 ALI1 AFeaces kfe * ALI1
_J17 ASITissue ALiver QSI * CSITissue / PSI
_J18 ABlood ASITissue QSI * CBlood
_J19 ABlood ALiver QL * CBlood
_J20 ALiver ABlood (QL + QSI) * CLiver / PL
_J21 ABlood ARest QRest * CBlood
_J22 ARest ABlood QRest * (ARest / Rest) / PRest
_J23 ASITissue ASITissueMet1 VmaxSIMet1 * (CSITissue / PSI) / (KmSIMet1 + CSITissue / PSI)
_J24 ALI1 ALI1Met2 VmaxLIMet2 * CLI1 / (KmLIMet2 + CLI1)
_J25 ALI1 ALI1Met3 VmaxLIMet3 * CLI1 / (KmLIMet3 + CLI1)
_J26 ALiver ALiverMet2 VmaxLMet2 * (CLiver / PL) / (KmLMet2 + CLiver / PL)
_J27 ALiver ALiverMet3 VmaxLMet3 * (CLiver / PL) / (KmLMet3 + CLiver / PL)
_J28 ALiver ALiverMet1 VmaxLMet1 * (CLiver / PL) / (KmLMet1 + CLiver / PL)

ODEs

\(\frac{d[\mathtt{ASt}]}{dt} = - \mathit{ksto}\cdot \mathit{ASt}\)

\(\frac{d[\mathtt{ASI1}]}{dt} = \mathit{ksto}\cdot \mathit{ASt} - \mathit{kt1}\cdot \mathit{ASI1} - \mathit{kabsSI1}\cdot \mathit{CSI1}\)

\(\frac{d[\mathtt{ASI2}]}{dt} = \mathit{kt1}\cdot \mathit{ASI1} - \mathit{kt2}\cdot \mathit{ASI2} - \mathit{kabsSI2}\cdot \mathit{CSI2}\)

\(\frac{d[\mathtt{ASI3}]}{dt} = \mathit{kt2}\cdot \mathit{ASI2} - \mathit{kt3}\cdot \mathit{ASI3} - \mathit{kabsSI3}\cdot \mathit{CSI3}\)

\(\frac{d[\mathtt{ASI4}]}{dt} = \mathit{kt3}\cdot \mathit{ASI3} - \mathit{kt4}\cdot \mathit{ASI4} - \mathit{kabsSI4}\cdot \mathit{CSI4}\)

\(\frac{d[\mathtt{ASI5}]}{dt} = \mathit{kt4}\cdot \mathit{ASI4} - \mathit{kt5}\cdot \mathit{ASI5} - \mathit{kabsSI5}\cdot \mathit{CSI5}\)

\(\frac{d[\mathtt{ASI6}]}{dt} = \mathit{kt5}\cdot \mathit{ASI5} - \mathit{kt6}\cdot \mathit{ASI6} - \mathit{kabsSI6}\cdot \mathit{CSI6}\)

\(\frac{d[\mathtt{ASI7}]}{dt} = \mathit{kt6}\cdot \mathit{ASI6} - \mathit{kt7}\cdot \mathit{ASI7} - \mathit{kabsSI7}\cdot \mathit{CSI7}\)

\(\frac{d[\mathtt{ALI1}]}{dt} = \mathit{kt7}\cdot \mathit{ASI7} - \mathit{kabsLI}\cdot \mathit{CLI1} - \mathit{kfe}\cdot \mathit{ALI1} - \frac{\mathit{VmaxLIMet2}\cdot \mathit{CLI1}}{\mathit{KmLIMet2}+\mathit{CLI1}} - \frac{\mathit{VmaxLIMet3}\cdot \mathit{CLI1}}{\mathit{KmLIMet3}+\mathit{CLI1}}\)

\(\frac{d[\mathtt{ASITissue}]}{dt} = \mathit{kabsSI1}\cdot \mathit{CSI1} + \mathit{kabsSI2}\cdot \mathit{CSI2} + \mathit{kabsSI3}\cdot \mathit{CSI3} + \mathit{kabsSI4}\cdot \mathit{CSI4} + \mathit{kabsSI5}\cdot \mathit{CSI5} + \mathit{kabsSI6}\cdot \mathit{CSI6} + \mathit{kabsSI7}\cdot \mathit{CSI7} - \frac{\mathit{QSI}\cdot \mathit{CSITissue}}{\mathit{PSI}} + \mathit{QSI}\cdot \mathit{CBlood} - \frac{\mathit{VmaxSIMet1}\cdot \frac{\mathit{CSITissue}}{\mathit{PSI}}}{\mathit{KmSIMet1}+\frac{\mathit{CSITissue}}{\mathit{PSI}}}\)

\(\frac{d[\mathtt{ALiver}]}{dt} = \mathit{kabsLI}\cdot \mathit{CLI1} + \frac{\mathit{QSI}\cdot \mathit{CSITissue}}{\mathit{PSI}} + \mathit{QL}\cdot \mathit{CBlood} - \frac{(\mathit{QL}+\mathit{QSI})\cdot \mathit{CLiver}}{\mathit{PL}} - \frac{\mathit{VmaxLMet2}\cdot \frac{\mathit{CLiver}}{\mathit{PL}}}{\mathit{KmLMet2}+\frac{\mathit{CLiver}}{\mathit{PL}}} - \frac{\mathit{VmaxLMet3}\cdot \frac{\mathit{CLiver}}{\mathit{PL}}}{\mathit{KmLMet3}+\frac{\mathit{CLiver}}{\mathit{PL}}} - \frac{\mathit{VmaxLMet1}\cdot \frac{\mathit{CLiver}}{\mathit{PL}}}{\mathit{KmLMet1}+\frac{\mathit{CLiver}}{\mathit{PL}}}\)

\(\frac{d[\mathtt{ABlood}]}{dt} = - \mathit{QSI}\cdot \mathit{CBlood} - \mathit{QL}\cdot \mathit{CBlood} + \frac{(\mathit{QL}+\mathit{QSI})\cdot \mathit{CLiver}}{\mathit{PL}} - \mathit{QRest}\cdot \mathit{CBlood} + \frac{\mathit{QRest}\cdot \frac{\mathit{ARest}}{\mathit{Rest}}}{\mathit{PRest}}\)

\(\frac{d[\mathtt{ARest}]}{dt} = \mathit{QRest}\cdot \mathit{CBlood} - \frac{\mathit{QRest}\cdot \frac{\mathit{ARest}}{\mathit{Rest}}}{\mathit{PRest}}\)

\(\frac{d[\mathtt{AFeaces}]}{dt} = \mathit{kfe}\cdot \mathit{ALI1}\)

\(\frac{d[\mathtt{ASITissueMet1}]}{dt} = \frac{\mathit{VmaxSIMet1}\cdot \frac{\mathit{CSITissue}}{\mathit{PSI}}}{\mathit{KmSIMet1}+\frac{\mathit{CSITissue}}{\mathit{PSI}}}\)

\(\frac{d[\mathtt{ALI1Met2}]}{dt} = \frac{\mathit{VmaxLIMet2}\cdot \mathit{CLI1}}{\mathit{KmLIMet2}+\mathit{CLI1}}\)

\(\frac{d[\mathtt{ALI1Met3}]}{dt} = \frac{\mathit{VmaxLIMet3}\cdot \mathit{CLI1}}{\mathit{KmLIMet3}+\mathit{CLI1}}\)

\(\frac{d[\mathtt{ALiverMet2}]}{dt} = \frac{\mathit{VmaxLMet2}\cdot \frac{\mathit{CLiver}}{\mathit{PL}}}{\mathit{KmLMet2}+\frac{\mathit{CLiver}}{\mathit{PL}}}\)

\(\frac{d[\mathtt{ALiverMet3}]}{dt} = \frac{\mathit{VmaxLMet3}\cdot \frac{\mathit{CLiver}}{\mathit{PL}}}{\mathit{KmLMet3}+\frac{\mathit{CLiver}}{\mathit{PL}}}\)

\(\frac{d[\mathtt{ALiverMet1}]}{dt} = \frac{\mathit{VmaxLMet1}\cdot \frac{\mathit{CLiver}}{\mathit{PL}}}{\mathit{KmLMet1}+\frac{\mathit{CLiver}}{\mathit{PL}}}\)

Assignment rules

variable assignment
SI1 VSI1
SI2 VSI2
SI3 VSI3
SI4 VSI4
SI5 VSI5
SI6 VSI6
SI7 VSI7
LI1 BW * VMB
SITissue BW * VSITissuec
Liver BW * VLc
Blood BW * VBc
Rest VRest
VSITissue VSITissuec * BW
VL VLc * BW
VB VBc * BW
VSI1 VSI
VSI2 VSI
VSI3 VSI
VSI4 VSI
VSI5 VSI
VSI6 VSI
VSI7 VSI
VRest 0.84 * BW - VL - VB - VSITissue
QC 15 * pow(BW, 0.74)
QL QLc * QC
QSI QSIc * QC
QRest (1 - QLc - QSIc) * QC
Papp_in_vivo pow(10, 0.6836 * PappCaco2_log - 0.5579) * 3600 / 10
kabsSI1 Papp_in_vivo * SASI
kabsSI2 Papp_in_vivo * SASI
kabsSI3 Papp_in_vivo * SASI
kabsSI4 Papp_in_vivo * SASI
kabsSI5 Papp_in_vivo * SASI
kabsSI6 Papp_in_vivo * SASI
kabsSI7 Papp_in_vivo * SASI
kabsLI Papp_in_vivo * SAinb
SI VSITissuec * 1000
VmaxSIMet1 VmaxSIMet1c / (1000 * 60 * S9SI * SI * BW)
VmaxLIMet2 VmaxLIMet2c / 1000000 * 1000 * VMB * BW
VmaxLIMet3 VmaxLIMet3c / 1000000 * 1000 * VMB * BW
L VLc * 1000
VmaxLMet2 VmaxLMet2c / 1000000 * 60 * VLS9 * L * BW
VmaxLMet3 VmaxLMet3c / 1000000 * 60 * VLS9 * L * BW
VmaxLMet1 VmaxLMet1c / 1000 * 60 * VLS9 * L * BW
CSI1 ASI1 / SI1
CSI2 ASI2 / SI2
CSI3 ASI3 / SI3
CSI4 ASI4 / SI4
CSI5 ASI5 / SI5
CSI6 ASI6 / SI6
CSI7 ASI7 / SI7
CSITissue ASITissue / SITissue
CLiver ALiver / Liver
CBlood ABlood / Blood
CLI1 ALI1 / (VMB * BW)
SITissueMet1 VmaxSIMet1 * (CSITissue / PSI) / (KmSIMet1 + CSITissue / PSI)
L1Met2 VmaxLIMet2 * CLI1 / (KmLIMet2 + CLI1)
L1Met3 VmaxLIMet3 * CLI1 / (KmLIMet3 + CLI1)
LiverMet2 VmaxLMet2 * (CLiver / PL) / (KmLMet2 + CLiver / PL)
LiverMet3 VmaxLMet3 * (CLiver / PL) / (KmLMet3 + CLiver / PL)
LiverMet1 VmaxLMet1 * (CLiver / PL) / (KmLMet1 + CLiver / PL)

Parameters

id name unit model qualifier
BW Bodyweight kg http://purl.obolibrary.org/obo/PBPKO_00008
VLc Volume fraction of liver dimensionless http://purl.obolibrary.org/obo/PBPKO_00078
VBc Volume fraction of blood dimensionless http://purl.obolibrary.org/obo/PBPKO_00104
VSITissuec Volume fraction of small intestine tissue dimensionless http://purl.obolibrary.org/obo/PBPKO_00072
VMB Feces fraction to bodyweight dimensionless not specified
VSITissue Volume of small intestine tissue L not specified
VL Volume of liver L http://purl.obolibrary.org/obo/PBPKO_00077
VB Volume of blood L http://purl.obolibrary.org/obo/PBPKO_00108
VSI Volume of small intestine L http://purl.obolibrary.org/obo/PBPKO_00071
VSI1 Volume of small intestine L http://purl.obolibrary.org/obo/PBPKO_00071
VSI2 Volume of small intestine L http://purl.obolibrary.org/obo/PBPKO_00071
VSI3 Volume of small intestine L http://purl.obolibrary.org/obo/PBPKO_00071
VSI4 Volume of small intestine L http://purl.obolibrary.org/obo/PBPKO_00071
VSI5 Volume of small intestine L http://purl.obolibrary.org/obo/PBPKO_00071
VSI6 Volume of small intestine L http://purl.obolibrary.org/obo/PBPKO_00071
VSI7 Volume of small intestine L http://purl.obolibrary.org/obo/PBPKO_00071
VRest Volume of rest of body L http://purl.obolibrary.org/obo/PBPKO_00105
QSIc Cardiac output fraction to small intestine dimensionless http://purl.obolibrary.org/obo/PBPKO_00019
QLc Cardiac output fraction to liver dimensionless http://purl.obolibrary.org/obo/PBPKO_00025
QC Cardiac output L/h http://purl.obolibrary.org/obo/PBPKO_00013
QL Cardiac output to liver L/h http://purl.obolibrary.org/obo/PBPKO_00024
QSI Cardiac output to small intestine L/h http://purl.obolibrary.org/obo/PBPKO_00018
QRest Cardiac output to rest of body L/h http://purl.obolibrary.org/obo/PBPKO_00050
PL Partition coefficient blood-liver dimensionless http://purl.obolibrary.org/obo/PBPKO_00577
PSI Partition coefficient blood-small intestine dimensionless http://purl.obolibrary.org/obo/PBPKO_00574
PRest Partition coefficient blood- rest body dimensionless http://purl.obolibrary.org/obo/PBPKO_00585
ksto stomach emptying rate /h not specified
kt1 Transfer rate to next compartment within the intestine /h not specified
kt2 Transfer rate to next compartment within the intestine /h not specified
kt3 Transfer rate to next compartment within the intestine /h not specified
kt4 Transfer rate to next compartment within the intestine /h not specified
kt5 Transfer rate to next compartment within the intestine /h not specified
kt6 Transfer rate to next compartment within the intestine /h not specified
kt7 Transfer rate to next compartment within the intestine /h not specified
kfe Transfer rate to feces /h http://purl.obolibrary.org/obo/PBPKO_00236
PappCaco2_log logaritmic Papp caco 2 value cm/h not specified
Papp_in_vivo effective Papp Caco 2 not specified not specified
SASI Surface area per intestinal compartment dm^2 http://purl.obolibrary.org/obo/PBPKO_00010
kabsSI1 Absorption rate constant L/h http://purl.obolibrary.org/obo/PBPKO_00142
kabsSI2 Absorption rate constant L/h http://purl.obolibrary.org/obo/PBPKO_00142
kabsSI3 Absorption rate constant L/h http://purl.obolibrary.org/obo/PBPKO_00142
kabsSI4 Absorption rate constant L/h http://purl.obolibrary.org/obo/PBPKO_00142
kabsSI5 Absorption rate constant L/h http://purl.obolibrary.org/obo/PBPKO_00142
kabsSI6 Absorption rate constant L/h http://purl.obolibrary.org/obo/PBPKO_00142
kabsSI7 Absorption rate constant L/h http://purl.obolibrary.org/obo/PBPKO_00142
SAinb Surface are of large intestine dm^2 http://purl.obolibrary.org/obo/PBPKO_00010
kabsLI Absorption rate from large intestine L/h http://purl.obolibrary.org/obo/PBPKO_00142
MW Molecular weight g/mol http://purl.obolibrary.org/obo/PBPKO_00127
S9SI Scaling factor small intestinal S9 protein yield mg/g not specified
SI Small intestine to bodyweight g/kg http://purl.obolibrary.org/obo/PBPKO_00072
VmaxSIMet1c Vmax constant not specified http://purl.obolibrary.org/obo/PBPKO_00212
VmaxSIMet1 Vmax not specified http://biomodels.net/SBO/SBO_0000027
KmSIMet1 Kinetic constant umol/L http://biomodels.net/SBO/SBO_0000027
VmaxLIMet2c Vmax constant not specified http://purl.obolibrary.org/obo/PBPKO_00212
VmaxLIMet3c Vmax constant not specified http://purl.obolibrary.org/obo/PBPKO_00212
VmaxLIMet2 Vmax not specified http://biomodels.net/SBO/SBO_0000027
VmaxLIMet3 Vmax not specified http://biomodels.net/SBO/SBO_0000027
KmLIMet2 Kinetic constant umol/L http://biomodels.net/SBO/SBO_0000027
KmLIMet3 Kinetic constant umol/L http://biomodels.net/SBO/SBO_0000027
VLS9 Scaling factor liver S9 protein yield mg/g not specified
L Volume fraction of liver g/kg http://purl.obolibrary.org/obo/PBPKO_00078
VmaxLMet2c Vmax constant not specified http://purl.obolibrary.org/obo/PBPKO_00214
VmaxLMet3c Vmax constant not specified http://purl.obolibrary.org/obo/PBPKO_00214
VmaxLMet1c Vmax constant not specified http://purl.obolibrary.org/obo/PBPKO_00214
VmaxLMet2 Vmax not specified http://biomodels.net/SBO/SBO_0000027
VmaxLMet3 Vmax not specified http://biomodels.net/SBO/SBO_0000027
VmaxLMet1 Vmax not specified http://biomodels.net/SBO/SBO_0000027
KmLMet2 Kinetic constant umol/L http://biomodels.net/SBO/SBO_0000027
KmLMet3 Kinetic constant umol/L http://biomodels.net/SBO/SBO_0000027
KmLMet1 Kinetic constant umol/L http://biomodels.net/SBO/SBO_0000027
CSI1 Concentration in small intestine mg/L not specified
CSI2 Concentration in small intestine mg/L not specified
CSI3 Concentration in small intestine mg/L not specified
CSI4 Concentration in small intestine mg/L not specified
CSI5 Concentration in small intestine mg/L not specified
CSI6 Concentration in small intestine mg/L not specified
CSI7 Concentration in small intestine mg/L not specified
CSITissue Concentration in small intestine tissue mg/L not specified
CLiver Concentration in liver mg/L http://purl.obolibrary.org/obo/PBPKO_00539
CBlood Concentration in blood mg/L http://purl.obolibrary.org/obo/PBPKO_00301
CLI1 Concentration in large intestine mg/L not specified
SITissueMet1 not specified not specified not specified
L1Met2 not specified not specified not specified
L1Met3 not specified not specified not specified
LiverMet2 not specified not specified not specified
LiverMet3 not specified not specified not specified
LiverMet1 not specified not specified not specified